In a serial investigation of the effects of immunisation with S. mutans in rhesus monkeys maintained on a "human" type of cariogenic diet, the numbers of S. mutans in cervical plaque, crevicular-fluid washings, fissures of teeth, and in saliva were lower in immunised animals than in sham-immunised controls. Immunisation also caused a delay in initial colonisation and a slowing of the rate of colonisation with S. mutans. These bacteriological changes were associated with a reduction in the smooth-surface-caries score. No relationship was found between the presence of S. sanguis and caries, but there was an inverse relationship between the proportions of S. mutans and S. sanguis isolated. Increased titres of complement-fixing, haemagglutinating and precipitating antibodies to S. mutans were found in the sera of immunised but not of control monkeys. A significant increase in salivary haemagglutinating antibodies was not detected. The results suggest that immunisation with S. mutans causes an increase in serum antibodies and a reduction in the number of S. mutans in the oral flora, and that these are associated with a reduction in dental caries.