The present investigation was conducted to study metabolic and hormonal responses to prolonged exercise to exhaustion in insulin-dependent diabetic subjects. Sixteen healthy subjects (control) and 15 diabetics with no-insulin administration for 12 hours were studied. They were submitted to short-term exercise to exhaustion on a cycle ergometer at 55% to 60% of maximum oxygen consumption (VO2max). Exercise tolerance was significantly lower in diabetic subjects (66 +/- 6.7 v 117 +/- 9.4 minutes), and glucose concentration was significantly higher in these subjects. At exhaustion, only diabetic subjects showed a significant decrease in glycemia (142 +/- 20 v 111 +/- 16 mg/dL). Lactate concentration increased significantly during exercise up to 30 minutes, but at exhaustion only control subjects showed a reduction. No significant difference in free fatty acid (FFA) concentrations was observed between the groups during a 30-minute exercise period; however, at exhaustion levels were significantly higher in control subjects. Prolactin and C-peptide concentrations were significantly lower in diabetic subjects, whereas glucagon concentration was higher. No significant differences between the groups were observed for cortisol and growth hormone (GH) concentrations. We conclude that (1) diabetic subjects show reduced exercise tolerance when no insulin is administered for 12 hours, and (2) exercise to exhaustion reduces serum glucose concentrations in insulin-dependent diabetics.