A study of a tetravalent live oral rhesus rotavirus vaccine was conducted in 26 healthy infants 6-22 weeks of age to evaluate safety, viral shedding, and immunogenicity in a double-blind, placebo-controlled fashion. The tetravalent rhesus rotavirus vaccine (RRV-TV) contained equal amounts of RRV (serotype 3) and the VP7 reassortants DxRRV (serotype 1), DS1xRRV (serotype 2), and ST3xRRV (serotype 4). RRV-TV was highly infectious; 16 of 18 recipients shed virus. However, the recovered virus was almost exclusively the parent rhesus strain, RRV. Humoral immune responses were largely limited to the RRV strain. The most consistent response, seen in 14 of 18 vaccines, was an ELISA IgM response to purified RRV. Mucosal antibody responses were not seen. The limited immune response may be a function of age, presence of maternal antibody, timing of the convalescent specimens, or the polyvalent nature of the vaccine.