Caliciviruses have, for the 1st time, been shown experimentally to infect a primate. Twenty-four hours after being inoculated with San Miguel sea lion virus (SMSV), an African green monkey developed a febrile response and vesicular lesions at injection sites. Virus was recovered from lesion material 96 hours later and from the stool at 48 hours. Possible human infection with SMSV was indicated by serologic evidence. Three persons working with 4 distinct serotypes of SMSV developed neutralizing antibody titers to 2 SMSV types. The positive serum-neutralization test results were confirmed, using immunoelectron microscopy to demonstrate complexes of viruses and antibodies.