An in vitro study assessing the metabolic response of growth-plate cartilage explants to mechanical stress was performed. Cultured explants were exposed to two types of stress: (a) single high-compressive force (SHC), and (b) multiple intermittent low-compressive force (MILC). Proliferative activity and matrix synthesis were determined with liquid scintillation counting after explants were labeled with [3H]thymidine and [35S]-sulfate. Our in vitro findings suggest that too high a force, even acting for a short time, may result in permanent injury of growth plate cartilage. Hence, we hypothesized that there might be an unknown pathogenetic mechanism of Salter's fifth-type epiphyseal injury. We report the results of our study.