A randomized placebo-controlled double-blind field trial of RIT 4237 attenuated rotavirus vaccine in Lima, Peru, evaluated the protection against diarrheal illness by one, two, or three doses of vaccine. There were 391 children, 2-18 months old, studied for the occurrence of diarrhea during the 18 months after vaccination. Three doses of the vaccine provided 40% protection against any diarrheal illness associated with rotavirus alone but 58%-75%; protection against the more severe rotaviral illnesses. The vaccine appeared to be more efficacious when it was administered to children in the first year of life. Three doses provided up to 89% efficacy against more severe diseases due to serotype 1 rotavirus, and one dose also afforded significant protection. The protection was lower, even with three doses, against serotype 2 rotavirus. This vaccine trial has provided important insights on how such trials should be conducted and on the serotype-specificity of protection from rotavirus infection. Future vaccines should be able to protect against severe disease caused by all rotavirus serotypes and must work in developing countries where rotavirus is the most important cause of diarrheal mortality.