The syndrome of progressive ischemic gangrene (PIG) of the extremities was examined over 3.5 years in patients undergoing maintenance dialysis (MD) in Kuwait and was compared to that in a similar age group (>40 years) in the general population. The incidence of PIG in MD patients was 15.4/1000 person years of observation (PYO) versus 0.086/1000 PYO in the general population. Patients with diabetes mellitus were found to be at particular risk. PIG developed in 41.4/1000 PYO of diabetic patients who received MD, compared to 7.1/1000 in nondiabetic patients on MD and 0.14/1000 in diabetics without renal disease. The clinical, biochemical, radiological, and histological findings in the 8 patients who developed PIG while on maintenance dialysis (MD) are presented. Two patients had severe hyperparathyroidism and their histological findings were consistent with systemic calciphylaxis. Histological examination, in the remaining patients, showed severe calcified atherosclerosis. Intimal hypertrophy was common especially in patients with long duration on dialysis. The three lesions produced a variable degree ofluminal narrowing and were associated with arterial thrombosis. None of the patients showed evidence of iron deposition even in those with systemic calciphylaxis and excessive iron stores. Our study indicated a high incidence of PIG in patients undergoing MD, especially in those with diabetes mellitus. These findings constitute a cogent argument in favor of early parathyroidectomy in selected cases and concern with long-term consequences of atherosclerosis in this patient population.