Agents that elevate intracellular concentrations of cAMP in cultured spleen cells can augment the in vitro 19s humoral immune response to SRBC. DBcAMP and 8BrcAMP were more effective than MIX, CT, PGE1, or ISO in producing the enhanced PFC response, when they were present only during an early stage of immune induction. The thesis is presented that the differential ability of these agents to augment humoral immunity results from their relative ability to maintain elevated concentrations of intracellular cAMP. Studies on the cellular mechanism by which cAMP elevation produces immune enhancement reveal that DBcAMP effects are on a T-cell-deficient population of murine spleen cells (predominantly B cells and macrophages). In addition, we showed that DBcAMP cannot replace the need for helper T cells in the induction of the PFC response to SRBC. Taken collectively, these results suggest that cAMP may be an important immunoregulatory signal, and that a variety of pharmacologic agents that modulate the induction of the humoral immune response may operate via this as a final common biochemical pathway.