We conducted an open clinical trial to determine whether administration of iloprost, a stable prostacyclin analog, has any effect on urinary albumin excretion and other parameters associated with non-insulin-dependent diabetes mellitus (NIDDM) patients. Twenty-three NIDDM patients with nephropathy were divided into groups A and B which were matched in terms of sex, age, duration of diabetes and blood glucose control. After 2 weeks of observation, 11 patients in group A received an intravenous infusion of iloprost (10 micrograms at a rate of 0.075 microgram/kg per h) once daily for 2 weeks, while 12 untreated diabetic patients in group B served as controls. In group A, iloprost significantly reduced the urinary albumin excretion rate, the urinary albumin-creatinine ratio and N-acetyl-beta-D-glucosaminidase without decreasing creatinine clearance during the treatment period (P < 0.05, respectively). However, none of these parameters changed significantly in group B. Urinary beta 2-microglobulin, blood pressure, heart rate, serum electrolytes, BUN and serum creatinine were not significantly altered by iloprost during the treatment period. Side effects associated with iloprost were mild and could be ameliorated by slowing the infusion rate. We conclude that iloprost appears to be safe and has an apparent effect on the urinary albumin excretion rate and N-acetyl-beta-D-glucosaminidase.