C57BL/6 and BALB/c mice were infected intravenously with 10(7) Mycobacterium lepraemurium (MLM). At various times after infection, spleen cells were tested for their capacity to proliferate in vitro in response to concanavalin A (ConA) and to allogeneic cells. The generation of alloreactive cytotoxic T lymphocytes was also studied. The mitogen- and allogeneic-cell-induced blastogenesis of splenocytes from MLM-infected C57BL/6 and BALB/c mice was shown to be depressed during infection. The maximal decrease occurred 6 months after infection. Conversely, no reduction in the ability to generate alloreactive cytotoxic T lymphocytes was observed even after 6 months of infection. At the same time, interleukin 2 (IL2) activity generated by ConA stimulation of infected splenocytes was measured in both strains. IL2 activity in the ConA-stimulated culture supernatants was decreased as early as 1 month after MLM inoculation as compared with supernatants from age-matched control mice. Thus, IL2 production by infected-mouse spleen cells was shown to decline earlier than their proliferative responses to ConA and to allogeneic cells. ConA-induced T-cell blasts from infected mice showed a reduced ability to proliferate when incubated with an IL2-containing reference supernatant from ConA-stimulated normal spleen cells. These data suggest that a defect in IL2 production and utilization might contribute to the impairment of T cell-mediated immunity observed in MLM-infected mice.