Salicylates suppress net glycosaminoglycan synthesis in articular cartilage. The inhibitory effect is greater in osteoarthritic (OA) cartilage than in normal cartilage. Whether the isolated OA chondrocyte is inherently more susceptible to the effects of salicylate on glycosaminoglycan metabolism has not been determined. The results of this study show that, after isolation from the extracellular matrix, normal and OA chondrocytes in suspension culture are similarly susceptible to the metabolic effects of salicylate. However, chondrocytes from the contralateral knees of dogs with unilateral OA were notably resistant to the effects of salicylate.