In this investigation it has been demonstrated that specific growth factors are able to modify collagen secretion in explants from healing rabbit medial collateral ligaments. The addition of 2.5 ng transforming growth factor beta 1 (TGF-beta 1)/mL to 3-week-old scar explants resulted in an increase in the total amount of collagen secreted. Analysis of collagen types I and III individually revealed that the increase mediated by TGF-beta 1 was due primarily to an increase in collagen type I secretion. This led to a ratio of type I:type III that is closer to that found in normal ligament tissue. The addition of 100 ng insulin-like growth factor 2 (IGF-2) to explant cultures of 3-week-old scar tissue also led to an increase in the quantity of collagen secreted, but the increase was in both type I and III collagens. These effects were observed to a lesser degree in 6-week-old scar tissue, and by 12 weeks postinjury, minimal effects of the growth factors on collagen synthesis was detected. Neither growth factor influenced collagen secretion by normal ligament or synovium. In contrast, IGF-1 (100 ng/mL) or basic fibroblast growth factor (bFGF) (10 ng/mL) did not exert a detectable effect on collagen secretion by any of the normal or healing tissues. These results indicate that TGF-beta 1 and IGF-2 can modify the metabolic activity of cells in explants of healing ligaments early after injury and may enhance the repair process leading to improved function.