Six Type 1 (insulin-dependent) diabetic subjects were studied in order to determine the contribution of recycling of glucose carbon to the overproduction of glucose which is characteristic of the fasting hyperglycaemia produced by insulin withdrawal. The subjects were studied on two occasions, once after an overnight insulin infusion and once following 24 h of insulin withdrawal. The difference in turnover rates of 1-14C-glucose and 3-3H-glucose was used as a measure of glucose recycling. Insulin withdrawal caused a marked metabolic derangement with a rise in non-esterified fatty acids from 0.69 +/- 0.23 to 1.11 +/- 0.21 mmol/l (mean +/- SEM, p less than 0.05), total ketones from 0.27 +/- 0.06 to 2.06 +/- 0.51 mmol/l (p less than 0.01), cortisol from 341 +/- 43 to 479 +/- 31 nmol/l (p less than 0.05) and growth hormone from 1.1 +/- 0.3 to 19 +/- 5 mu/l (p less than 0.05). Glucose turnover rose from 13.8 +/- 2.3 mumol.kg-1.min-1 at a glucose of 6.9 +/- 0.7 mmol/l in the insulin infused study to 25.8 +/- 4.4 mumol.kg-1.min-1 (p less than 0.05) at a glucose of 16.4 +/- 0.7 mmol/l in the insulin withdrawn study. Recycling also rose from 3.0 +/- 0.4 mumol.kg-1.min-1 to 9.4 +/- 2.2 mumol.kg-1.min-1 (p less than 0.05) when insulin withdrawn, accounting for 23 +/- 3% and 36 +/- 3% of glucose turnover, respectively. We conclude that in the severely insulin deficient Type 1 diabetic subject recycling of glucose carbon is a major contributor to the excess glucose production.