In order to determine whether interleukin 6 (IL-6) is involved in the pathogenesis of the cartilage destruction observed in arthritis, the effect of human recombinant IL-6 on collagenase production and proteoglycan synthesis by bovine articular chondrocytes was examined. Addition of IL-6 (1.0 to 1000 U/ml) to the culture medium did not stimulate collagenase production or alter proteoglycan secretion. Whereas human purified interleukin 1 (IL-1) (20 U/ml) stimulated collagenase production and inhibited proteoglycan synthesis. Furthermore addition of IL-1 (20 U/ml) to chondrocyte cultures did not stimulate the chondrocytes to produce IL-6. Under our experimental conditions, IL-6 did not stimulate chondrocytes to proliferate as measured by [3H] thymidine incorporation. This would suggest that IL-6 is not involved in mediating cartilage loss.