Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid. Preclinical studies have indicated that meloxicam has potent anti-inflammatory activity, together with a good gastrointestinal and renal tolerability profile. This report summarizes studies undertaken to compare meloxicam to other NSAIDs in the inhibition of the inducible cyclooxygenase (COX-2) in inflamed areas (pleurisy of the rat, peritonitis of mice) and their influence on the activity of the constitutive cyclooxygenase (COX-1) in stomach, kidney, brain, and blood. In pleurisy of the rat, meloxicam was twice as potent as tenoxicam, 3 times as potent as flurbiprofen, 8 times as potent as diclofenac, and 20 times as potent as tenidap at inhibiting prostaglandin E2 (PGE2) biosynthesis. In the peritonitis model in mice, meloxicam was approximately twice as active as piroxicam, and more than 10 times as active as diclofenac in the suppression of PGE biosynthesis. Doses of meloxicam sufficient to inhibit PGE2 biosynthesis in the pleural exudate and peritoneal exudate had no influence on leukotriene-B4 (LTB4) or leukotriene-C4 (LTC4) content. The effect of meloxicam on the PGE2 content of rat gastric juice and rat urine was weaker than that of piroxicam or diclofenac. Meloxicam was a weaker inhibitor of the increased PGE2 concentration in brain of rats and mice (induced by convulsant doses of pentetrazole) than piroxicam, diclofenac, or indomethacin. Meloxicam had a weaker effect on serum thromboxane-B2 (TXB2) concentration in rats than piroxicam or tenoxicam. The in vivo findings confirm the results of in vitro tests, conducted separately, showing that meloxicam preferentially inhibits COX-2 over COX-1. COX-2 is the inducible isoenzyme implicated in the inflammatory response, whereas COX-1 has cytoprotective effects in the gastric mucosa. Therefore, a preferential selectivity for one isoenzyme over another, as displayed by meloxicam, may have implications in the clinical setting in terms of a more favorable risk: benefit profile.