Post-glucose enhancement of insulin action may represent a physiological mechanism for the acute regulation of insulin sensitivity of target tissues. To clarify whether a similar mechanism is operative in the insulin-resistant diabetic state we have investigated the effects of a mixed meal on adipocyte insulin action in eight patients with Type 2 diabetes mellitus. Ninety minutes after ingestion of breakfast insulin binding to fat cells increased by 21% (p less than 0.05). In the fasting state 6 patients had a significant response of glucose transport and lipogenesis to insulin whereas two exhibited non-responsiveness. In the 6 responders insulin sensitivity, as estimated by the insulin concentration at which half-maximal effect was achieved, increased for glucose transport (before, 260 +/- 46 pmoll-1; after, 105 +/- 21 pmol l-1; p less than 0.05) and for lipogenesis (before, 36 +/- 9 pmol l-1; after, 9 +/- 2 pmol l-1; p less than 0.05). No significant changes occurred in basal or maximal glucose transport or lipogenesis. In the two primary non-responders intake of the meal was associated with average increase in maximal insulin responsiveness of 52% for glucose transport and 28% for lipogenesis. Intake of a mixed meal is associated with a slight increase of insulin binding to adipocytes from patients with Type 2 diabetes mellitus but a marked increase of adipocyte insulin sensitivity at the post-binding levels of glucose transport and metabolism.