Muscle blood flow and capillary diffusion capacity were determined in 21 Type 1 (insulin-dependent) diabetic patients and in 12 age-matched healthy subjects by measuring the simultaneous clearance of 133xenon and 131iodide from hyperaemic anterior tibial muscle. Blood flow was significantly lower (mean +/- SD: 46.7 +/- 14.1 versus 59.4 +/- 12.9 ml 100 g-1 min-1, p less than 0.02) and capillary diffusion capacity was significantly greater (mean +/- SD: 8.0 +/- 2.1 versus 5.9 +/- 1.3 mol/min, p less than 0.005) in the diabetic patients than in the control subjects. Ultrastructural dimensions and density of capillaries in the gastrocnemius muscle of 11 diabetic patients and six control subjects were also studied. Diabetic and control capillaries did not differ in total capillary area. Compared with normal capillaries, the percentage area of basement membrane and the apparent basement membrane thickness were significantly greater (1.21 +/- 0.6 versus 0.78 +/- 0.2 mu, p less than 0.05) in diabetic capillaries, while there were no significant differences in luminal, endothelial and pericytial areas. There was no difference in capillary density between the two groups. No correlation was found between basement membrane thickness and capillary diffusion capacity in the diabetic patients. We conclude that the greater capillary diffusion capacity is due to increased permeability of diabetic capillaries, and that the basement membrane is probably not rate-limiting in the transcapillary transport of hydrophilic substances in diabetic subjects.