A new oral hypoglycemic agent, acetohexamide, is compared with four other sulfonylurea drugs in 70 patients with diabetes mellitus, the majority of whom had had either primary or secondary failure with other oral hypoglycemic compounds.Of the 70 patients studied, 43 per cent responded to acetohexamide, maintaining fasting blood sugar levels under 160 mg. per 100 ml. Only 24 per cent of the 70 patients maintained fasting blood sugar levels under 120 mg. per 100 ml. The primary response to acetohexamide was equal to or better than that noted in the patients treated with chlorpropamide, tolbutamide, azepinamide, and cycloheptolamide. Approximately 25 per cent of patients who had failed to respond to other sulfonylurea compounds responded to acetohexamide.Preliminary studies reveal no serious toxicity. No consistent effects on serum cholesterol levels or thyroid activity were noted.