The effect of conventional treatment on insulin action in subcutaneous adipose tissue was studied in 6 patients with non-insulin-dependent diabetes mellitus (NIDDM). Insulin receptor binding and the effect of the hormone on glucose oxidation were determined before and after 6-14 months of treatment with diet plus sulphonylurea. Glycaemic control and in vivo insulin sensitivity were significantly improved by the treatment. Before treatment, the adipocyte insulin receptor binding and the sensitivity to insulin stimulation of adipose tissue glucose oxidation were normal and did not change after treatment. In contrast, the maximum insulin-induced glucose oxidation was markedly decreased before treatment, whereas it was totally normalized after treatment. The conclusion is that insulin resistance in adipose tissue of NIDDM subjects is solely due to post-receptor defects in insulin action. This resistance is completely off-set by conventional treatment with diet plus sulphonylurea.