Mesangial cell migration is a feature of certain renal diseases such as mesan-giocapillary glomemlonephritis, a disorder which responds to treatment with cyclo-oxygenase inhibitors. We undertook the present study to determine whether prostaglandin E2 (PGE2) might have a direct effect on mesangial cell migration. PGE2 (10–8M) treated cells migrated a mean percent area of 16.8 ± 0.5 during 24 h when compared to control cells which migrated only a mean percent area of 10.3 ± 0.8 (p < 0.001). At 48 h, PGE2-treated cells migrated a mean percent area of 21.7 ± 1.1 when compared to control cells which migrated only a mean percent area of 14.7 ± 1.4 (p < 0.01). Meclofenamate (10-5M), a cyclo-oxygenase inhibitor, significantly (p < 0.02) inhibited migration of mesangial cells (at 48 h controls 13.4 ± 0.5 vs. meclofenamate-treated cells 3.2 ± 0.8). Since meclofenamate attenuates basal production of PGE2 by mesangial cells, inhibition of migration by mesangial cells by meclofenamate indicates that the basal production of PGE2 by mesangial cells also significantly contributes to the migration of mesangial cells. 3-Isobutyl-l-methylxanthine (IBMX, 10–3M), a phosphodiesterase inhibitor, also significantly (p < 0.001) enhanced migration of mesangial cells (controls 13.4 ± 0.5 vs. IBMX-treated cells 20.8 ± 0.5). These results suggest that mesangial cell migration is directly enhanced by PGE2. The present study provides a rationale for the use of cyclo-oxygenase therapy in patients with mesangiocapillary glomemlonephritis.