Calves were given (s.c. inoculations) viable M. bovis with and without Freund''s complete adjuvant (FCA). In the calves given M. bovis with FCA, immediate and delayed cutaneous reactivity to formolized M. bovis and increases in serum indirect hemagglutination (HA) titers were pronounced. None of the calves showed evidence of an anamnestic response to a 2nd inoculation of M. bovis. Treatment of the test serums from all calves with 2-mercaptoethanol (2-ME) revealed the presence of increased immunoglobulin M-IHA activities throughout the 70-day postinoculation (PI) period. Strong cell-mediated responses, as shown by the lymphocyte-activation test, were not observed until PI day 44. Lymphocytes from calves given M. bovis with FCA gave the greatest response to M. bovis antigens. The lymphocyte activation response to M. bovis rapidly decreased after day 44 PI. The in vitro lymphocyte responses to phytohemagglutinin (PHA), as well as the control rates of lymphocyte incorporation of tritiated thymidine, appeared to be depressed as a result of the M. bovis inoculations. The aqueous supernatant of M. bovis was generally suppressive to in vitro lymphocyte blastogenesis. M. bovis appeared to affect the immune responsiveness of the host directly by stimulation of suppressor cell function or transiently depressing T[thymus-derived]lymphocyte activities. The addition of FCA with M. bovis had an enhancing effect on humoral and cell-mediated responses probably by increasing macrophage presentation of antigen to T lymphocytes. The delayed development of cell-mediated immune responses may assist in the explanation of why some hosts are unsuccessful in mounting an effective immune response against M. bovis.