Substance P (SP), vasoactive intestinal polypeptide (VIP), and somatostatin content in rectal mucosa were determined by radioimmunoassay (RIA) in 38 diabetic patients (12 with normal bowel function, 13 with diabetic diarrhea, and 13 with constipation) and in 10 nondiabetic controls with normal bowel function. SP content (picograms per milligram) in the rectal mucosa of diabetics with normal bowel function was significantly higher than that of nondiabetic controls (P < .05). SP content in the rectal mucosa of diabetics with diabetic diarrhea and constipation was significantly lower than in diabetics with normal bowel habits and nondiabetic controls (P < .05). No differences were found in the rectal mucosa content of VIP and somatostatin between the different groups of diabetics and controls. Diabetic diarrhea is a condition with an intermittent nature and frequently alternates with constipation. Our findings showing low levels of rectal mucosa SP in both conditions suggest a possible common role of SP in the pathogenesis of diabetic diarrhea and constipation.