Turnover rates of glucose and free fatty acids were measured, using 3H-glucose and 14C-l-palmitic acid as tracers, in insulin-requiring diabetic patients at presentation and after insulin treatment. Correlations were sought with rates of substrate oxidation, determined independently from respiratory exchange, and with plasma hormone concentrations. The rates of appearance of glucose and of free fatty acids were increased in the diabetics to 17.6 and 10.2 micronmol min-1 kg-1 respectively. Both rates fell to normal (13.3 and 7.1 micronmol min-1 kg-1) after insulin. In the untreated state there was an inverse relationship between the rates of utilisation of glucose and free fatty acids (r = 0.61; p less than 0.05). It is suggested that this relationship represents the impairment of peripheral glucose utilisation by free fatty acids and by ketone bodies in vivo, so far only demonstrated in vitro. The tracer calculated rates of glucose utilisation correlated well over a wide range with the respiratory quotient in untreated diabetics, while respiratory quotient was inversely related to free fatty acid turnover rates. In untreated diabetics plasma cortisol and 3,3', 5'-triiodothyronine (rT3) were increased whereas thyroxine and 3,5,3'-triiodothyronine (T3) were decreased. 3,5,3'-Triiodothyronine concentration was closely related to the metabolic clearance rate of glucose (p less than 0.05), while cortisol concentrations correlated with glucose production (p less than 0.02) and blood ketone body concentration (p less than 0.02). It is concluded that glucose overproduction is the major contributor to the hyperglycaemia of untreated diabetes.