In this investigation we have demonstrated that specific growth factors are able to modify plasminogen activator (PA) activity in explants from both normal and healing ligaments. Specifically, the addition of insulin-like growth factor 2 (IGF-2; 100 ng/mL) and transforming growth factor beta 1 (TGF-beta 1; 2.5 ng/mL) to explants of unoperated and healing ligaments resulted in a decrease in both PA and PA--PA-binding protein complex in conditioned medium from several tissues, and particularly in medial collateral ligament (MCL) scar tissue. This effect was observed in the explants from 3-, 6-, and 12-week healing scar tissue. In addition, IGF-2 and TGF-beta 1 influenced PA release from MCL tissue derived from the unoperated knee joint of 3-week healing animals. In contrast, basic fibroblast growth factor (b-FGF; 10 ng/mL) and IGF-1 (100 ng/mL) did not cause a detectable alteration of PA and PA--PA-binding protein complex activity in any of the healing or unoperated ligaments analyzed. These results indicate that specific growth factors are able to modify the activity of cells in explants of ligament and healing ligament in a distinct manner.