In order to see if subcutaneous insulin treatment of type II diabetes might produce lasting physiologic changes, ten patients received one month's insulin treatment under strict dietary supervision. When compared to the pretreatment period, 48 hours after discontinuing insulin treatment fasting plasma glucose had fallen (P = 0.005), fasting serum insulin had risen (P = 0.005), and fasting hepatic glucose production measured by 3H-3-glucose turnover had fallen (P = 0.008). The metabolic clearance rate of glucose measured with the glucose clamp rose significantly after treatment at insulin infusion rates of 40 mU m-2 min-1 (P = 0.015) and 400 mU m-2 min-1 (P = 0.012). The serum insulin and C-peptide responses to oral glucose improved after the treatment in association with the improvement in glucose tolerance, but the plasma glucose response was unchanged. Six other type II diabetic patients who received only dietary supervision did not show significant changes in these variables. Six weeks after discontinuing insulin, the patients' fasting hepatic glucose production was still reduced compared to pretreatment (P = 0.028) and insulin action was still improved at both the lower (P = 0.028) and the higher (P = 0.028) insulin infusion rates, but the fasting plasma glucose and insulin and C-peptide responses to oral glucose had returned to pretreatment values. The improvement in glucose tolerance and beta-cell function induced by insulin treatment seems to be of more limited duration than the improvements in basal hepatic glucose production and in insulin action.