Monocyte phenotype heterogeneity is often associated with functional differences between the distinguished Mphi subpopulations. We have previously demonstrated that the Mphi subpopulation separated and stimulated by rosetting Mphi via the Type I Fc gamma R (CD64) are poor antigen presenting cells but can be induced to greater production of TNF alpha, IL-6 and PGE2 than the Fc gamma RI- Mphi population. Here we demonstrate that the Fc gamma RI- Mphi represent the major antigen presenting Mphi population and that APC capacity of the FcRI- Mphi can be further increased by elevating intracellular cAMP levels. Treatment of the Fc gamma RI+ Mphi with db cAMP decreases both their expression of CD64 and their capacity to produce TNF alpha to the levels typical of Fc gamma RI- Mphi. Db cAMP treatment of the Fc gamma RI+ Mphi subpopulation, however, cannot augment the antigen presenting capacity of this low APC Mphi subpopulation to the level of that of the Fc gamma RI- Mphi. Basal expression of the Mo3 activation marker was comparable in the FcRI+/FcRI- Mphi subpopulations, but the FcRI+ Mphi were induced by db cAMP treatment to increase their Mo3 expression to higher levels than the FcRI- Mphi. These results suggest that although elevated intracellular cAMP levels can modulate some Fc gamma RI+ Mphi functions to more closely parallel those of the Fc gamma RI- Mphi, this treatment cannot increase the efficiency of the Fc gamma RI+ Mphi subpopulation as an antigen presenting cell.