We have measured the formation of prostacyclin (PGI₂) in the rat gastric mucosaex vivo following oral administration of indomethacin, protacine and sodium salicylate (SS). It has been found that protacine, like indomethacin but in contrast to SS, markedly reduces PGI₂ synthesis as measured by inhibition of ADP-induced platelet aggregation. Parallel gastro-ulcerogenic studies demonstrate that protacine has very weak gastric irritancy when compared with indomethacin. In addition, the effect of these drugs has been evaluated on thromboxane B₂ (TXB₂) release by human polymorphonuclears (PMNs) stimulated with A23187 ionophorein vitro. It has been shown that protacine, like indomethacin, strongly inhibits cyclooxygenase activity as measured by radioimmunoassay of TXB₂. SS partially prevents the inhibitory effect of either