The findings in 676 patients treated with tolbutamide and chlorpropamide for periods of up to four years are presented. Only small differences between the results obtained with the 2 drugs were found. In twenty patients treatment was discontinued because of intercurrent disease or because of side effects. There were 67 primary failures (10%). Of the remaining 589, there were 66 secondary failures (11%), fifty-eight achieved fair control (10%) and 465 good control (79%). Satisfactory results were obtained most often in patients weighing between 85% and 115% of their standard weight, in those over 45 years of age, and in those who had not previously required insulin. The mean body weight of the patients increased by 1.3% while they were receiving sulfonylureas. Needle core liver biopsies were obtained from 8 patients. Four of these were normal, three showed focal collections of chronic inflammatory cells, and one showed early portal cirrhosis.