Mesangial hypercellularity is usually found in many models of nephritis characterized by monocyte/macrophage infiltration of the glomerulus. In order to examine the mechanism mediating these events, an in vitro model was used to study the effects of macrophage products on mouse mesangial cells, cultured under conditions which would render them relatively quiescent. Under these conditions, macrophage supernatants stimulated the proliferation of the mesangial cells. The stimulatory effect could be shown to be due in part to enhancement of endogenous mesangial cell PGE production. This was demonstrated by experiments which showed that macrophage supernatants stimulated mesangial cell PGE production, that the stimulatory effect of macrophage products was abrogated by pretreatment of mesangial cells with indomethacin, and finally that exogenous PGE2 stimulated mesangial cell proliferation.