Signal transduction through ligation of the CD23 (Fc epsilon RII) molecule was analysed in human B cells and monocytes. Monoclonal antibodies directed against the IgE binding site of CD23 were found to trigger phosphoinositide hydrolysis and calcium mobilization in B cells, but not in monocytes. These early events were also obtained with an IgE+anti-IgE complex, which supposedly mimicks the physiological situation of a multivalent antigen inducing the cross-linking of cell-bound IgE. Redistribution of CD23 was also found to evoke cAMP accumulation both in B lymphocytes and monocytes. Moreover, we present evidence indicating a possible cross-talk between the IL-4- and CD23-induced second messengers. We suggest that the alternative transduction pathways elicited by ligation of CD23 are linked to the CD23 isoform(s) expressed by these cells and may result from their association with different sets of molecules.