The role of prostaglandins in mediating the hemodynamic response to nitroglycerin in vivo is controversial. To determine the effect of inhibiting prostaglandin production on the response to nitroglycerin, either placebo or aspirin (650 mg) was administered 1 hour prior to the administration of nitroglycerin (432 micrograms) sublingually to 40 healthy volunteers in a double-blind, randomized, cross-over study. Prior to nitroglycerin administration, blood pressure and pulse rate were determined noninvasively every 2 minutes until stable conditions were reached, and then after nitroglycerin administration determinations were made every 1 minute for the first 10 minutes, every 2 minutes for the next 10 minutes, and every 5 minutes until 30 minutes had elapsed. At peak response in the placebo study, nitroglycerin lowered systolic pressure from 117 +/- 10 to 111 +/- 10 mm Hg (p less than 0.0001). Unexpectedly, nitroglycerin increased diastolic pressure from 75 +/- 8 to 80 +/- 7 mm Hg (p less than 0.005), thus reducing pulse pressure significantly. Pulse rate after nitroglycerin increased from 72 +/- 11 to 85 +/- 14 (p less than 0.001). Aspirin slightly modified the pattern of response at 1 minute but altered neither the peak hemodynamic responses nor the areas under the time-pressure and time-pulse curves. Thus nitroglycerin-induced prostaglandin production does not play a major role in the systemic hemodynamic response to nitroglycerin in vivo.