Soluble antigen preparations from Mycobacterium leprae are reported to inhibit the response to other stimuli, of peripheral blood mononuclear cells from lepromatous leprosy cases (BL/LL) and also from tuberculoid cases (TT/BL) and normal donors. We confirm these findings and in addition, report that a similar suppressive effect is exerted by antigen from Mycobacterium vaccae, Mycobacterium nonchromogenicum and, to a lesser extent, Mycobacterium tuberculosis and Mycobactyerium kansasii. Moreover, suppression is seen using peripheral blood mononuclear cells from individuals unlikely to have encountered the organism used. The suppression is not due to toxicity of the antigen preparation, and is not indomethacin sensitive. It involves a cell found in the E-rosetting population, which loses its ability to suppress or be suppressed, after 48 hr in culture. Possible explanations include a pharmacological effect of cell wall peptidoglycolipids, or the triggering of suppressor cells specific for common mycobacterial antigens.