We studied the effect of piroxicam, a long acting inhibitor of platelet aggregation, on the evolution of neuropathy in diabetic rats. We treated half of the rats with piroxicam and serially studied sensory and motor nerve conduction during 20 weeks of diabetes. The sensory nerve action potential amplitude was the same in treated and untreated rats before diabetes, and declined steadily as duration of diabetes increased. In treated rats, the amplitude fell more slowly and by 16 weeks and thereafter was significantly higher than in untreated rats. Sensory conduction velocity and motor nerve conduction studies were not affected by piroxicam treatment. The results suggest that piroxicam may slow the rate of progression of neuropathy in diabetic rats, probably by inhibiting platelet aggregation.