The effect of prostaglandin E1 (PGE1) on the renin-aldosterone system was investigated in hospitalized patients with non-insulin-dependent diabetes mellitus presenting with continuous proteinuria but without nephrotic syndrome. Of the 20 patients studied, 10 had continuous positive proteinuria > or = 200 mg/day and 10 had continuous positive proteinuria < 200 mg/day. Prostaglandin E1 (40 micrograms in 100 ml normal saline) was infused intravenously over 2 h twice daily for 4 weeks. Plasma renin activity (PRA) and the plasma aldosterone concentration (PAC) were determined by radioimmunoassay at 0 and 120 min after a frusemide injection given before the start of PGE1 treatment and during administration of PGE1 in week 4. The patients who had proteinuria < 200 mg/day showed significant decreases in the PRA0 and the ratio of PRA120:PRA0 and a decrease in the PAC120 during prostaglandin PGE1 administration. When the results for the two patient groups were combined, both the PAC120 and the PRA120 were found to be significantly lowered during administration of PGE1. The results indicate that PGE1 may be valuable in the treatment of diabetic nephropathy, since the compound inhibited the increased reactivity of the renin-aldosterone system in patients with non-insulin-dependent diabetes mellitus.