Although the Gianotti-Crosti syndrome (GCS) is regularly associated with hepatitis B infection elsewhere, in North America that association is rarely made. Accordingly, we studied nine children with acral, symmetrical eruptions typical of GCS for evidence of other infections. All were negative for hepatitis B surface antigen. Viral cultures were done in nine patients, and viruses isolated in two. One patient with a respiratory prodrome had respiratory syncytial virus (RSV) isolated, and a second patient studied simultaneously showed serological evidence of RSV infection. A third patient with both respiratory tract and gastrointestinal tract symptoms yielded a polio-vaccine enterovirus. Two patients with fever and pharyngitis had group A βhemolytic streptococci isolated from the throat. Skin biopsies were done in three cases, and findings were consistent with GCS. Electron microscopy of two lesional biopsy specimens failed to demonstrate viral particles. Epstein-Barr virus serological findings were negative in six cases and showed evidence of past infection in three cases. This study strengthens the observation that hepatitis B is not the causative agent of GCS in this country and suggests that multiple infectious agents may be associated with this distinctive exanthem.