The healing responses of the anterior cruciate ligament and the patellar tendon differ markedly. The anterior cruciate ligament fails to heal, whereas the patellar tendon heals slowly. The basis of these differences is unknown. Since cellular proliferation is a critical element of healing, we investigated the response to explants of anterior cruciate ligament and patellar tendon from sheep knees to platelet-derived growth factor-AB and transforming growth factor beta 1 as a function of time and dose. Explants cultured for 48, 72, and 96 hours with transforming growth factor beta 1 (0-100 ng/ml) or platelet-derived growth factor-AB (0-200 ng/ml) were radiolabeled for the final 24 hours with [3H]thymidine, and DNA synthesis was quantified as trichloroacetic acid-precipitable radioactivity normalized to dry tissue weight. Statistical analyses (analysis of variance) showed that transforming growth factor beta 1 induced a significant proliferative response in the anterior cruciate ligament at 96 hours with equivalent responses at 10, 50, and 100 ng/ml, whereas the patellar tendon only responded to one condition, 10 ng/ml at 96 hours. Conversely, the patellar tendon had a significant dose-dependent response to platelet-derived growth factor-AB at 72 and 96 hours, whereas the anterior cruciate ligament showed no proliferative response to platelet-derived growth factor-AB. The minimal response of anterior cruciate ligament to platelet-derived growth factor-AB could explain, at least in part, the poor repair capacity of this tissue. The response of the anterior cruciate ligament to transforming growth factor beta suggests that exogenous transforming growth factor beta may promote initial healing. Although growth factors have the potential to modulate soft-tissue repair, tissue responses in tendons and ligaments may vary at different anatomic sites.