The generation of an immune response involves the interaction of monocytes and T cells, but the events which regulate this interaction are not well understood. Culture of human peripheral blood monocytes in vitro induces low level surface expression of the p55 protein of the IL-2R and the expression of this receptor can be enhanced significantly by exposure to IFN-gamma. The addition of IL-2 to IFN-gamma-treated monocytes was shown to augment subsequent IL-1 beta secretion in the presence or absence of LPS. These effects could be partially blocked by anti-p55-IL-2R mAb. Nuclear "run on" assays and Northern analysis to probe for IL-1 beta transcripts showed enhanced IL-1 beta gene transcription and mRNA accumulation by monocytes treated with IFN-gamma and IL-2 but not in cultures that were obtained from monocytes treated with IL-2 alone. These results suggest that the T cell lymphokines IFN-gamma and IL-2 may act in a sequential fashion on monocytes to amplify the immune response by establishing a positive feedback circuit.