Basic fibroblast growth factor is a potent mitogen for chondrocytes and influences the protein synthesis of their extracellular matrix in vitro. To investigate its effect on normal developing articular cartilage in vivo, we injected basic fibroblast growth factor once into the knee joints of 4-week-old rats. Phosphate buffered saline was similarly injected into the contralateral knee joints as controls. A histological analysis showed that an injection of basic fibroblast growth factor induced enlargement of the articular cartilage area, especially in the condylar ridge region on day 7 after the injection. The extent of the enlargement was dose-dependent. The localization and amount of proliferating cells in the articular cartilage were analyzed immunohistochemically by the detection of proliferating cell nuclear antigen. On day 1 after the injection, the number of cells positive for proliferating cell nuclear antigen increased significantly in the joints that were injected compared with the controls, and Northern blot analysis showed that the level of messenger RNA for alpha 1(II) procollagen was lower in these joints than in the controls. The message in the joints that had been injected increased on day 7, and it was greater than that in the controls. This suggests that proliferating chondrocytes in developing articular cartilage respond to basic fibroblast growth factor with a resulting proliferation of chondrocytes followed by enlargement of cartilage.