The oral route of immunization with Streptococcus mutants was compared with the subcutaneous route in rhesus monkeys. Significant levels of serum IgG, IgM and IgA antibodies in Strep. mutans were elicited only in monkeys immunized subcutaneously. Similarly, the skin delayed hypersensitivity reaction to Strep. mutans was elicited only in the subcutaneously immunized monkeys. Oral immunization induced a modest increase in salivary IgA antibodies to Strep. mutans, though a slight increase in IgA antibodies was also found in the saliva of all other groups of immunized and control monkeys. A small though not significant reduction in dental caries was found in the monkeys immunized orally, whereas subcutaneous immunization with Strep. mutans consistently elicited a significant reduction in caries. Oral feeding of Strep. mutans failed to induce tolerance to a subsequent subcutaneous challenge by the same organism. Furthermore, sequential subcutaneous followed by oral immunization had little effect on the titre of salivary or serum antibodies.