The cell surface expression of the CD32 receptors for the Fc portion of immunoglobulin G (Fc gamma RII-CD32) is regulated by agents such as phorbol esters (PMA) and cytokines. In this study, we investigated the effects of PMA and interferon-gamma (IFN-gamma) on the expression of CD32C mRNA in U937 cells. When U937 (CD32+) cells are incubated with either PMA or IFN-gamma a significant enhancement of CD32C mRNA expression is observed with maximum enhancement at 18 hrs post-PMA and IFN-gamma addition. The addition of actinomycin D (ActD), a transcriptional inhibitor, together with either PMA or IFN-gamma diminishes the enhanced levels of CD32C mRNA to the basal levels, indicating that transcriptional regulation is involved in this modulatory process. The addition of cyclohexamide (CX), a protein synthesis inhibitor, to cultures undergoing stimulation with either PMA or IFN-gamma, increased the levels of CD32C mRNA synthesis suggesting that regulatory degradation proteins may be involved. The PMA and IFN-gamma stimulated CD32C mRNA is degraded within 2 hr post-stimulation and this degradation is delayed by the inhibition of de novo protein synthesis. These results, taken together with our previous studies of CD32A mRNA regulation in U937 cells stimulated with PMA, indicate that both the CD32A and C isomer mRNAs are rapidly degraded; however, CD32A and C isomer mRNAs are differentially regulated. At the optimal PMA dose, the time of mRNA stimulation of CD32A and C mRNA varies and the addition of CX to U937 cells together with PMA enhanced the levels of CD32C mRNA but had no effect on CD32A mRNA levels. These results imply that the differential regulation of the two CD32 isomers may result in differential function.