Picardo made his feature film debut as Eddie Quist, the serial killer werewolf in the Joe Dante film The Howling (1981). He also had a recurring role in the sitcom Alice and played a Doctor on an episode of The Golden Girls. He played a number of roles in Dante's family science fiction film Explorers (1985), and later appeared in Dante's The 'Burbs, Looney Tunes: Back in Action, Matinee, Gremlins 2: The New Batch, Small Soldiers and Innerspace. Picardo often plays roles under layers of prosthetic latex, having also played the swamp-dwelling Meg Mucklebones in Ridley Scott's film Legend. He also had a small role as a funeral Director in John Landis's Amazon Women on the Moon. He voices Pfish in two Pfish & Chip shorts as seen on Cartoon Network's What-A-Cartoon! Show. Picardo also portrays the voice and face of the robotic Johnny Cab in Total Recall. He appeared in one episode of ER in 1995 as Abraham Zimble (Season 2 - Episode 6, "Days Like This").