Tolfenamic acid (Clotam) has been used in the therapy of rheumatic diseases for some years. Regarding its chemical structure it belongs to the group of fenamates. The effect of tolfenamic acid on the synthesis of collagen and proteoglycans in granulation tissue, skin or cartilage of rat weanlings was tested and compared with the action of mefenamic acid. According to the results obtained, tolfenamic acid is a potent inhibitor of collagen as well as proteoglycan syntheses. The concentrations of the constituents of proteoglycans, i.e. protein core, link protein as well as glycosaminoglycans were decreased in the tissue after treatment with tolfenamic acid. In comparison with mefenamic acid, if the same doses were used (50 mg and 100 mg/kg of body weight/day in in vivo experiments and 10 mg/g wet tissue in in vitro experiments), tolfenamic acid exhibits more distinct inhibitory effect. A general inhibitory effect of tolfenamic acid on proteosynthesis is suggested.