The relationship between the production of interleukin-1 (IL-1) and interleukin-2 (IL-2) after stimulation of human mononuclear cells within an antigenic extract from Candida albicans was analyzed in both responder and nonresponder donors. Culture supernatants from responders contained both IL-1 and IL-2 activity, whereas the supernatants from nonresponders contained only IL-1 and no appreciable IL-2. However, the addition of exogenous IL-2 to nonresponder cultures restored the normal proliferative response. Similar observations were made when cells from mice infected intravenously with high doses of Mycobacterium bovis BCG were cultured; these cells showed a marked impairment of the proliferative response to purified protein derivative. Spleen cells from BCG-induced unresponsive mice failed to produce IL-2 despite the fact that normal IL-1 activity was present in the culture. Again, the addition of exogenous IL-2 fully reversed the proliferative unresponsiveness. Thus, the presence of IL-1 does not necessarily induce production of IL-2, and the proliferative unresponsiveness is therefore due to a primary lack of IL-2.