Twelve maturity-onset diabetic subjects were treated with chlorpropamide once daily, glibenclamide once daily, or glibenclamide twice daily in a crossover design study. Doses were increased until the fasting blood glucose concentrations became less than 6 mmol/L (108 mg/dl), at which time the patients were admitted for a 24-h study period. There was little difference between the plasma glucose and insulin responses to chlorpropamide or glibenclamide given twice daily (mean doses 489 and 11 mg/day, respectively). When glibenclamide was given once daily (mean dose 9 mg/day), similar plasma glucose concentrations during the day were obtained with slightly higher plasma glucose concentrations during the night. Four patients had chlorpropamide-induced flushing with alcohol, and six patients had postprandial hypoglycemia on glibenclamide. Chlorpropamide once daily or glibenclamide twice daily are suitable for control based on fasting blood glucose measurements.