To evaluate cell-mediated immune responses in patients infected with atypical mycobacteria (AM), mononuclear cells from patients were examined in vitro for purified protein derivatives (PPD) induced lymphocyte proliferation using combination of monoclonal antibodies and flowcytometry. Those from normal tuberculin-positive controls and chronic excreters with tuberculosis (chronics) were also examined. The results obtained were as follows: 1) In normal controls, PPD-S induced a significant proliferation of activated T cell subsets (Leu 4+ DR+, IL 2-R+ Leu 3+ and IL 2-R+ Leu 2+). A significant increase in pan T cells (Leu 4+), helper T cells (Leu 3+ 8-), suppressor T cells (Leu 2+ 15+) and B cells (Leu 4- DR+) was also observed. 2) In chronics, the pattern and degree of lymphocyte proliferation by PPD-S were similar to that observed in normal controls. 3) In AM, we found a significant proliferation of activated T cells (Leu 4+ DR+, IL 2-R+ Leu 3+, IL 2-R+ Leu 2+) and B cells (Leu 4- DR+) by PPD-S. However, the degree of lymphocyte proliferation in AM was clearly depressed as compared to normal controls and chronics. 4) In chronics, lymphocyte proliferation by PPD-S was significantly higher than that by PPD-B. In contrast, lymphocyte response by PPD-S was almost same as that by PPD-B in AM.