Jeff Foxlove is an ace advertising copywriter for the Cudmore Advertising Agency, an agency notorious for churning out crass, vulgar, and raunchy advertising campaigns. Jeff masters the art of writing tasteless advertising copy and has no reservations about wallowing in the mud of sleazy advertising; he makes a good salary and has attracted the attention and affection of an aspiring but dimwitted actress. Life is good for Jeff Foxlove.

However, all that is about to change. The turning point in Jeff's life comes when he vacations in the Yucatan. While exploring the dense jungle on a moonlit night, Jeff is savagely attacked and bitten by a mysterious, feral creature of the night. He manages to escape from the clutches of the beast, and the next morning, he is amazed to find that his wounds have miraculously healed. Jeff returns to New York City assuming that he can resume his normal life, but on the night of the next full moon, he experiences the agony of a horrible metamorphosis.

The magic of the full moon has transformed Jeff into a blood-thirsty werewolf and he roams the city looking for human prey. He finds two innocent victims in the park and attacks and kills them. The next morning he resolves to turn himself into the authorities, but his boss, the notorious schlock-monger, Damon Cudmore persuades him not to go to the authorities. He tells Jeff that he will find a way to keep the werewolf from killing again. Is this possible?

Werewolf On Madison Avenue is the story of Jeff's journey as both a werewolf and the genius behind a wildly successful advertising campaign. Can he be a werewolf during the night of the full moon and still keep his day job? Still, the thought of being a vicious killer-beast plague Jeff, and he becomes increasingly desperate to lift the curse of lycanthropy that is slowly consuming him. Jeff discovers that his only hope to become normal again is to return to the Yucatan jungle in search of a miracle cure.