The lapine articular chondrocyte monolayer was used to study the effects of cell proliferation, morphology, nd synthesis of proteoglycans of four nonsteroidal anti-inflammatory agents piroxicam, diclofenac sodium, sulindac sulfiphe, and indomethacin. None of the substances caused any alteration to chondrocyte morphology. Cell proliferation and macromolecular binding of 35SO4 were unaffected by piroxicam (0.2, 2, and 20 micrograms/ml) or diclofenac sodium (0.2, 2, and 5 micrograms/ml). Whereas indomethacin markedly reduced cell proliferation (100 mumol/l; p less than 0.01), it failed to alter net proteoglycan synthesis significantly (1, 10, and 100 mumol/l). Sulindac sulfiphe significantly reduced chondrocyte proliferation at 0.5 and 5 micrograms/ml (p less than 0.01). The 0.5 micrograms/ml concentration also markedly stimulated proteoglycan synthesis (171%; p less than 0.01). The use of the articular chondrocyte monolayer as an experimental model to investigate drug-induced alterations of cartilage metabolism is discussed.