The established, suppressive effect of salicylate on sulfated glycosaminoglycan (sGAG) synthesis by normal articular cartilage was reinvestigated using anatomically intact articular cartilage of the whole mouse patella. Employing the physiological murine sulfate concentration (1.0 mM) sodium salicylate (1-5 X 10(-3) M) caused a dose dependent inhibition of 35S-sGAG synthesis (10-35%). At a lower sulfate concentration (0.4 mM) this inhibition was increased (15-45%) and the suppression was even more pronounced in sulfate deprived medium. This observation stresses the need of using physiological sulfate concentrations in cartilage culture studies. In the presence of 100% serum the therapeutic drug concentration (1-2 X 10(-3) M) had no longer any suppressive effect, either at 1.0 mM or at any lower sulfate concentration. Our data suggest that salicylate has no direct effect on sGAG metabolism in normal articular cartilage in vivo and that adverse effects may be due to the observed salicylate induced lowering of the endogenous sulfate level.