Plasma beta-hydroxybutyrate (beta-OHB) concentrations and simultaneous urine tests for ketonuria (nitroprusside reaction) were evaluated every 4 h throughout a 24-h study in 10 healthy insulin-dependent diabetics who had poor control based on home urine tests and elevated hemoglobin A1C. Concurrent measurements of the major carbohydrate regulatory hormones were made in the diabetic group and in a control population of 20 age-matched subjects. In the diabetics, 73% of the beta-OHB measurements were elevated. Only 43% of the abnormal beta-OHB values were associated with ketonuria. The diabetic subjects also showed exaggerated diurnal patterns for plasma beta-OHB and cortisol. There were no significant differences for the other regulatory hormones in the diabetic and normal groups. We conclude that 1) abnormal plasma beta-OHB levels without ketonuria are prevalent in poorly controlled diabetics; 2) negative nitroprusside tests for ketonuria underestimate the presence of ketonemia due to increased beta-OHB concentrations; 3) both insulin deficiency and glucocorticoid excess may influence ketone body metabolism in insulin-dependent diabetic patients.