This paper investigates factors involved in mesangial cell (MC) proliferation by focussing on the proliferative effects of phorbol myristate acetate (PMA) on mouse MC in culture in comparison to those of fetal calf serum (FCS). The potential roles of cyclooxygenase and lipoxygenase products of arachidonic acid metabolism and of hydroxyl radicals on their proliferation are addressed. The results indicate: (1) that PMA can induce proliferation of MC; (2) that inhibition of prostaglandin synthesis by indomethacin does not modify PMA-induced proliferation but enhances the proliferative response to FCS, and (3) that stimulation of MC proliferation by PMA or FCS is inhibited by agents interfering with the generation of products of the lipoxygenase pathway and hydroxyl radical scavengers. The role of lipoxygenase products and reactive oxygen species in MC proliferation deserves further investigation.