Misfits rule in American Splendor, a magnificent biographical film about one particular loser with a winning glower. Harvey Pekar is a real-life Cleveland native who writes the text of underground comics based on his own experiences. He's as glum as they come.

As portrayed by Paul Giamatti with a sourpuss expression, Harvey never sugarcoats or sees a silver lining. Although you might not want to be his friend, you could always trust him to tell the truth -- albeit usually a sad truth. Happiness is not an option for someone so eternally pessimistic about the world and his place in it. While looking at his slumping, disheveled image in the mirror, he observes: "Now there's a reliable disappointment."

Yet, directors Shari Springer Berman and Robert Pulcini have crafted a movie that's anything but. American Splendor, now at the Roxy in Burlington, is as inventive, entertaining and emotionally fulfilling as any release this year. The husband-and-wife team, who also collaborated on the script, found a way to integrate the performers with the actual people and the art that depicts them.

The opening credits alone reveal great ingenuity. Comic book-like panels encompass still photographs of the characters, cinematography or drawings from Pekar's body of work, which extends back some 25 years.

Over a soundtrack of old-time blues, jazz and rock, Pekar's raspy voice narrates events recounted on the screen by the actors or by periodic use of his comics. And he shows up in person, at one point even in a behind-the-scenes sequence with Giamatti. Harvey's thoughts are occasionally articulated in cartoon balloons. While the juxtaposition of fact and artifice is jarring at first, it soon makes perfect sense. This feature brilliantly blends documentary immediacy and fanciful imagination.

Saddled with a dead-end day job as a file clerk in a hospital, Harvey befriends a developmentally challenged co-worker named Toby. Judah Friedlander delivers a remarkably accurate imitation of this genuine self-proclaimed nerd. Toby is obsessed with the film Revenge of the Nerds because he perceives an empowering geek-brotherhood message in the raunchy 1984 comedy.

Harvey finds solace from the isolation of geekdom in his love of comics and his vast collection of vintage recordings. As a teen, he and fellow Ohio resident Robert Crumb, played here by James Urbaniak, establish a bond based on these mutual outcast passions.

Desperate for a creative outlet, Harvey later begins keeping a sort of diary about his daily activities, most of them humiliating, frustrating or depressing. A chronicler of personal pain, he demonstrates a keen ear for dialogue heard on the streets, in supermarkets and at work. Crumb, who hits pay dirt as an artist ("Mr. Natural," "Fritz the Cat") after moving to San Francisco, illustrates his pal's proliferation of words. The comic book series American Splendor is published.

Twice divorced, Harvey remains mired in loneliness until a fan letter arrives from Joyce Brabner -- normally blonde Hope Davis as a brunette in oversize eyeglasses. When this strong-willed peace activist from Delaware visits him, she brings her own assortment of neurotic quirks, such as hypochondria and a habit of diagnosing other people's psychological problems. They are soul mates prone to squabbling, and quickly decide to marry.

Despite his reluctance to have children, her need to nurture eventually prompts the couple to adopt a daughter. It's a delight to watch Giametti's turn as a middle-aged grump awkwardly adjusting to the unlikely role of father.

Harvey faces a much more difficult hurdle when doctors discover a malignant tumor in his groin. Joyce encourages him to channel the fear and suffering into a graphic novel. They co-author Our Cancer Year, which goes on to earn a National Book Award.

His comics career, while never terribly lucrative, does lead to fame. Harvey is a frequent guest on "Late Night With David Letterman." The actual footage of their repartee is unsettling; they're both cranks, but the talk-show host often pokes fun at unglamorous folks. The laughter dies, along with the TV welcome mat, when Pekar angrily denounces NBC for the weapons manufactured by its parent company, General Electric.

Even without that confrontation, he is unable to relish his accomplishments. Left-leaning politics, disdain for bourgeois values and a bleak temperament may be antithetical to sustained success. To borrow a catchphrase from Crumb, Harvey Pekar, at least the cinematic version, can only "keep on truckin'." But, in doing so, his reliable disappointments seem strangely life-affirming.