Hormonal and metabolic changes were compared in five insulin-dependent diabetic men and five control men during a 3-h marathon-training run. Insulin was withheld 16-26 h before the start of the run, and a normal breakfast was finished 2.5 h before the start of the run. Blood glucose concentrations decreased significantly in the diabetic subjects but remained constant in the control subjects. During the run, plasma free fatty acids, beta-hydroxybutyrate, and alanine concentrations behaved similarly in both groups. Only postexercise ketosis was more pronounced in the diabetic subjects. Peripheral serum free-insulin concentrations were slightly lower in the diabetic subjects at the start of the study, but these insulin concentrations became significantly elevated afterward compared with the control subjects. Plasma glucagon levels increased in the diabetic but not in the control subjects. Growth hormone levels increased sharply and to significantly higher levels in the diabetic than in the control subjects, who presented a slow gradual increase. Plasma cortisol levels were slightly, but at some moments significantly, higher in the diabetic subjects. The plasma catecholamine concentrations increased in both groups but to significantly higher levels in the diabetic subjects. There is no evidence from this study for an insufficient secretion of counterregulatory hormones if a hypoglycemic reaction occurs during a long-distance run in reasonably well controlled, well-trained diabetic subjects without long-term complications.