Ultrastructural morphometry was used to quantify capillary basement membrane width, pericyte coverage of capillaries, pericyte degeneration, and the extent of acellular capillaries in skeletal muscle obtained at autopsy from neck, thigh, calf and foot of five male and four female diabetic subjects and an equal number of sex- and age-matched nondiabetic subjects. Within diabetic or nondiabetic subjects, the trend for all four parameters to increase in frequency or magnitude in the order neck less than thigh less than calf was highly significant; the only statistically significant difference between calf and foot muscles for any of the four parameters was capillary basement membrane width for nondiabetic subjects, which was significantly thinner in foot than in calf muscle (t = 2.45; p less than 0.05). Pericyte coverage of capillaries did not differ between diabetic and nondiabetic subjects for each muscle examined; however, capillary basement membrane width, the frequency of pericyte debris and acellular capillaries were increased significantly in the lower extremity muscles of diabetic compared to nondiabetic subjects, and the magnitude of the difference between these two groups increased in the order thigh less than calf less than foot. The observations that pericyte degeneration and acellular capillaries are present in skeletal muscle as well as in retinal microvessels suggest that common pathophysiological mechanisms may contribute to vascular disease in these two very different tissues. The additional finding that relative differences between diabetic and nondiabetic subjects, in the frequency and magnitude of these changes, increase in the order neck less than calf less than foot is consistent with the marked increase in peripheral vascular disease and gangrene in the lower extremities of diabetic patients.