The significance of T-cell activation in the immunopathogenesis of articular disease has been studied in an in vitro model to assess the capacity of phytomitogen-induced lymphokines to degrade cartilage matrix proteoglycans. Supernatants derived from T-cell activation of normal human peripheral blood lymphocytes were shown to contain a monocyte-dependent, serum-inhibitable, dialyzable factor or factors capable of inducing significant proteoglycan degradation, as assessed by release of macroprecipitable 35S-labeled proteoglycan from heterologous cartilage substrates.