Tolmetin [1-methyl-5-p-tolouylpyrrole-2-acetic acid (McN-2559, Tolectin)] and several of its analogs were shown to be potent inhibitors of the synthesis of prostaglandin E₂ from arachidonic acid by bovine seminal vesicle prostaglandin synthetase in vitro. Kinetic studies indicated that tolmetin, like indomethacin and aspirin, inhibited the synthetase competitively with respect to substrate. Unlike most non-steroidal anti-inflammatory agents, however, tolmetin was a competitive reversible inhibitor, and did not promote a time-dependent inactivation of the prostaglandin synthetase. Tolmetin and these other 1-methyl-pyrrole acetic acids represent a new structural class of anti-inflammatory agents which inhibit prostaglandin synthetase.