In view of the possible antiaggregation effects of newer general anesthetics we investigated the in vitro and in vivo effects of isoflurane and nitrous oxide on platelet aggregation. Platelets obtained from 18 healthy volunteers, were exposed in vitro for 30 min in a closed chamber to oxygen-carbon dioxide (90%, 5%) (control), oxygen-carbon dioxide-nitrous oxide (80%), or oxygen-carbon dioxide-isoflurane (1.5%) with or without nitrous oxide (80%). Samples were tested in ADP- and collagen-induced aggregation tests. Both nitrous oxide and isoflurane produced statistically significant inhibition of ADP-induced aggregation. Inhibition of collagen-induced aggregation was not statistically significant. In 18 patients who received nitrous oxide (3 L/min) and isoflurane (1-2%) during anesthesia, platelet aggregation was reduced significantly. We conclude that both nitrous oxide and isoflurane cause moderate but statistically significant inhibition of platelet aggregation that may be clinically important in some patients.