Endothelin-1 stimulated the release of bioassayable platelet-activating factor-like material and the incorporation of acetate to PAF in rat mesangial cells, in a dose-dependent manner, with an EC50 of about 10(-9) M. Endothelin-1 also stimulated dose dependently [3H]thymidine incorporation into DNA, protein synthesis and cell growth. The platelet-activating factor antagonists BN-52021 (10(-5) M), and alprazolam (10(-5) M), reduced significantly endothelin-1-stimulated thymidine incorporation into DNA, protein synthesis and cell growth. Platelet-activating factor also stimulated significantly thymidine incorporation into DNA, cell proliferation and protein synthesis. In conclusion, the present results suggest that endothelin-1 induces mesangial cell proliferation through a mechanism involving among others, synthesis and release of platelet-activating factor by these cells.