The immunodepressive effect of a single, carcinogenic dose of dimethylnitrosamine was tested in a potent model of renal cancer induction using two antigens which differ in their cellular processing. Responsiveness to sheep red blood cells (SRBC), an antigen requiring the collaboration of both thymus-dependent (T) and thymus-independent (B) lymphocytes was determined by a plaque-forming assay; antibody production to Brucella abortus antigen, a thymus-independent antigen, was measured in an agglutination test. The results suggested that DMN exerted little or no effect on B lymphocytes in the anti-Bruc antibody assay, but a substantial deleterious effect on T-B cell collaboration as assessed in the anti-SRBC antibody response. This effect commenced immediately following the carcinogenic insult from 24 h, with a degree of depression for the first 10 days equivalent to antilymphocyte globulin in terms of numbers of anti-SRBC antibody-forming cells. From 2 weeks there was gradual recovery with full restoration of normal responsiveness at 8 weeks. During the ensuing period of emergence of neoplastic foci in the kidney, and with the progression of such foci to tumors of macroscopic dimensions, there was no accompanying depression of antibody response. The differential effect was discussed in terms of selectivity of action, and lymphocyte subsets.