Pentoxifylline, a new trisubstituted methylxanthine derivative known for its hemorrheologic action, has been shown to improve exercise tolerance in atherosclerotic patients. We examined the responses of diabetic atherosclerotic patients to pentoxifylline administration, measured by Doppler waveform analysis and exercise tolerance. Standard exercise tolerance and Doppler waveform analytic studies of the lower extremity, specifically the right dorsalis pedis artery, were performed before and after three months of pentoxifylline administration (400 mg three times a day). The study group comprised ten subjects (six men and four women) with a mean (+/- SD) age of 60 +/- 3.3 years. Data were analyzed using a paired Student t test. All ten subjects showed a significant increase in exercise tolerance after pentoxifylline treatment. Eight of ten subjects demonstrated a significant increase in right dorsalis pedis arterial flow.