The mechanism of the anti-inflammatory activity of fepradinol (CAS 67704-50-1) has been investigated. The effect of fepradinol was compared with that of indometacin and other non-steroidal anti-inflammatory drugs. Oral dosing of fepradinol and cyproheptadine suppressed zymosan-induced paw edema in rats. Indometacin and piroxicam were without effect. Fepradinol inhibited the early and late stages of concanavalin A-induced edema in rats; indometacin and piroxicam only inhibited the late stage. Fepradinol and indometacin prevented the carrageenin-induced inflammation in rats: they acted on the exudate, on the increase of protein and gamma-glutamyltransferase levels, and also reduced the number of leucocytes. But, in contrast to indometacin, fepradinol did not inhibit prostaglandin E2 biosynthesis. Fepradinol and indometacin prevented diarrhoea induced by intravenous injection of endotoxin in mice or by oral administration of castor oil in rats. In in vitro tests, fepradinol did not inhibit prostaglandin biosynthesis from arachidonic acid by bovine seminal vesicle microsomal enzyme or 15-lipoxygenase. These results indicate that fepradinol possesses a potent inhibitory activity on the acute inflammation in rodents and that its anti-inflammatory activity does not seem to be related to an inhibitory effect on prostaglandin biosynthesis.