1 Low concentrations of meclofenamate, flufenamate or mefenamate had little effect on contractions in response to acetylcholine in any tissue studied. 2 Sodium meclofenamate potently antagonized contractions of guinea-pig ileum longitudinal muscle to prostaglandin E2 (PGE2), PGF2 alpha or PGD2. 3 In guinea-pig colonic longitudinal muscle, contractions to PGE2 were reduced by sodium meclofenamate, but contractions of the longitudinal or circular muscle to PGF2 alpha or PGD2 were less effectively inhibited. 4 In human gastrointestinal longitudinal muscle, sodium meclofenamate or flufenamate potently inhibited contractions to PGF2 alpha, but not to PGE2. 5 Sodium mefenamate or mefenamic acid, even in high concentrations, had little effect on contractions to PGF2 alpha, but tended to inhibit PGE2-induced contractions of human gastrointestinal longitudinal muscle. 6 The therapeutic advantages of prostaglandin synthesis inhibitors which also antagonize responses to certain prostaglandins are discussed.