Previous studies have shown that IL-2-stimulated peripheral blood mononuclear cells (PBMC) produce IL-1 beta and TNF alpha and that monocytes are the primary source of these IL-2-inducible cytokines. In this report, we provide evidence that monocytes are not the only source. We examined cytokine production by IL-2-treated, nonmonocytic PBMC and found that a population of nonadherent low-density cells (NLDC) produced both IL-1 beta and TNF alpha in response to IL-2. IL-1 beta was synthesized by IL-2-treated NLDC as the 35-kDa intracellular precursor (pro-IL-1 beta), but was neither secreted nor processed to the mature 17-kDa form of the molecule. To determine which cells within the NLDC population generated pro-IL-1 beta and TNF alpha in response to IL-2, we positively selected NK cells and T cells, the two major components of NLDC, using specific monoclonal antibodies. Although IL-2-treated CD16+ NK cells produced TNF alpha and transcribed IL-1 beta mRNA, they did not synthesize the IL-1 beta protein. Conversely, LPS-treated CD16+ and IL-2-treated CD4+ and CD5+ NLDC produced elevated levels of both TNF alpha and IL-1 beta. Our findings illustrate the complex nature of IL-1 beta production by IL-2-stimulated PBMC and suggest that the factors controlling IL-1 beta gene transcription and translation, as well as secretion and processing, vary widely as a function of cell type and stimulus.