Several non-steroidal anti-inflammatory drugs (NSAIDs) were studied for their effects on normal and damaged murine articular cartilage, both in vitro and in vivo. In vitro, in the absence of serum, sodium salicylate caused significant suppression of 35S-glycosaminoglycan (GAG) synthesis, whereas tiaprofenic acid, piroxicam, prednisolone sodium phosphate and several other NSAIDs were without effect. Trypsin-mediated proteoglycan depletion did not change the susceptibility of the articular chondrocyte to these drugs. Similarly, no enhancement of drug effect was seen when arthritic cartilage was taken from an acutely inflamed joint, and prenisolone sodium phosphate even seemed to diminish inflammation-mediated suppression of 35S-GAG synthesis. The short term in vivo effects of some of the drugs were tested in mice with unilateral zymosan-induced arthritis. At day 1 after arthritis induction, in vivo 35S-GAG synthesis by the cartilage of the arthritic joint was decreased to 63%. Only sodium salicylate suppressed in vivo 35S-GAG synthesis in the healthy and arthritic joint to the same extent in both. At day 28, GAG synthesis in the postarthritic joint was enhanced to 160%. This type of cartilage appeared to be more susceptible to drug effects, since all drugs tested showed clear suppression of the augmented GAG production in vivo. Finally, in vivo drug effects were tested on normal and enhanced 35S-GAG degradation, the latter in the zymosan-induced arthritic joint. Both tiaprofenic acid and prednisolone sodium phosphate appeared to suppress degradation in healthy and, to some extent, in arthritic cartilage.(ABSTRACT TRUNCATED AT 250 WORDS)