Adult-onset diabetics have markedly diminished or absent acute insulin responses to glucose that can be partially restored by sodium salicylate infusion. To determine whether this restoration of the acute insulin response is glucose dose dependent and whether complete restoration can be achieved, adult-onset diabetics with a mean fasting plasma glucose value of 216 ± 20 mg. per deciliter (x̄ ± S.E.) were stimulated with various doses of intravenous glucose. Restoration occurred in a glucose dose-dependent manner. Complete restoration could not be achieved with the maximal tolerable glucose dose (80 gm.). Second phase insulin secretion also improved in a glucose dose-dependent manner. These findings are compatible with the hypothesis that defective insulin secretion in adult-onset, hyperglycemic diabetics is not due to absolute deficiency of insulin but may be a result of defective recognition of glucose signals by pancreatic B-cells - a defect that can be partially reversed by sodium salicylate.