The effects of two nonsteroidal anti-inflammatory drugs (NSAIDs), Etodolac (ETO) and acetylsalicylic acid (ASA), used at pharmacological concentrations, were tested on several metabolic parameters of human chondrocytes cultivated in three-dimensional culture. The results indicated that proteoglycan synthesis was significantly decreased by ASA treatment, whereas Etodolac did not affect this parameter. Neither ASA nor Etodolac modified type-II collagen production. Both NSAIDs were potent inhibitors of PGE2 production, but Etodolac was more efficient at equimolar concentrations. In contrast, collagenolytic activity was unaffected by Etodolac.