In 14 normal subjects, treatment with acetylsalicylic acid (ASA, 3.2 g daily for 3 days) a well known inhibitor of prostaglandin synthesis, caused a slight but significant decrease (p is less than 0.05) in basal plasma glucose levels; by contrast, basal insulin rose from 5 +/- 1 to 8 +/- 1 muU/ml (p is less than 0.01) after ASA. Pretreatment with ASA augmented the early insulin response to a standard IV glucose tolerance test (25 g) in 7 normal subjects (p is less than 0.05 at 2 min; p is less than 0.02 at 5 min; p is less than 0.01 at 10 min). No significant changes were detected in the rate of glucose utilization. 7 additional subjects received a standard arginine test without and with ASA pretreatment. Arginine stimulated insulin levels were increased after ASA (p is less than 0.01 at 15 min; p is less than 0.05 at 30 min; p is less than 0.05 at 45 min), whereas glucose values were lower than under basal conditions at all times, with significant differences at 105 (p is less than 0.02) and 120 (p is less than 0.05) min. A possible role of prostaglandins upon the insulin responses to glucose and arginine is discussed.