Summary: Monomeric and heat-aggregated bovine γ globulin (BγG) were administered to normal adult rats by injection of doses between 0.02 and 20 mg directly into the thymus, cervical lymph nodes, spleen, or blood stream. On the same day or 12 or 35 days later, these animals and operated, non-injected controls were challenged with a standard footpad dose of BγG in complete adjuvant, followed by a secondary stimulus at 25 days. Formation of hemagglutinating and precipitating antibodies and the development of Arthus and delayed skin reactivities were evaluated in a quantitative manner. In general, soluble BγG was more effective than aggregated BγG in inhibiting immune responses. Tolerance produced by aggregated antigen increased strikingly between 0 and 12 days and tended to wane by 35 days. Injection by the intrathymic route was more effective in producing tolerance than injection by other routes.