The effects of acetylsalicylic acid (ASA), a known inhibitor of prostaglandin (PG) synthesis, on plasma glucose, insulin, glucagon and growth hormone (GH) responses to tolbutamide were examined in ten normal volunteers. Treatment with 3.2 g ASA daily for 3 days caused a significant reduction in basal plasma glucose levels (p less than 0.05); by contrast, basal insulin rose from 23 +/- 2 to 31 +/- 2 microU/ml (p less than 0.01). No significant changes in the basal concentrations of glucagon and GH were found after ASA. Insulin response to tolbutamide was significantly augmented after ASA (p less than 0.01) while GH response to hypoglycemia was reduced (p less than 0.05). The pattern of plasma glucose and glucagon was not significantly modified by the treatment. Since ASA seems to have an action opposite to PGE on insulin and GH secretion, it is possible that the ASA may work through inhibition of PG synthesis.