PURPOSE: Diabetes mellitus is one of the most common causes of erectile dysfunction (ED). The pathogenesis of ED in diabetic patients is not clear, although vasculogenic and neurogenic factors are involved. This study was designed to further characterize the pathophysiologic manifestations of ED in diabetic patients. MATERIALS AND METHODS: Fifty-seven important patients aged 20 to 71 (mean 45) years participated in this study. On the basis of their medical history, physical examination, and multidisciplinary impotence work-ups, patients were divided into diabetic (n=25) and non-diabetic (psychogenic; n=32) groups. To evaluate vasculogenic manifestations, a pharmacological erection test and penile duplex ultrasonography were performed. To evaluate neurologic manifestations, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining was performed on cavernous tissue samples obtained by percutaneous biopsy. Staining was assessed by counting the number of nitric oxide synthase (NOS)-containing nerve fibers present in four random fields (power 400x). In the diabetic group, we additionally assessed the duration of diabetes, the duration of treatment, and the latency between the onst of ED and the time diabetes was diagnosed. RESULTS: The pathophysiologic causes for ED in the diabetics proved to be neurogenic in 44%, vasculogenic in 20%, and mixed (combined neurogenic and vasculogenic) in 36%. Vascular assessment in the diabetics showed that penile rigidity was decreased and end-diastolic velocity was increased compared with the nondiabetics. Latency to the onset of ED from the diagnosis of diabetes was 0 to 15 (average 5.3) years, and it was closely correlated with the status of NOS-containing nerves (p<0.05). The status of NOS-containing nerves also correlated well with the degree of diabetic control but not with the control method. CONCLUSIONS: Diabetes causes ED by a variety pathophysiologic mechanisms, including neurogenic, vasculogenic, or both. Early and appropriate control of diabetes is required to prevent ED.