Growth plate histomorphometry of rats after spaceflight or on-Earth unloading showed marked alterations in cell organization (D. Montufar-Solis et al., J. Appl. Physiol., 73, 19S, 1992; D. Montufar-Solis and J. Duke, Am. Soc. Gravitational Space Biol., 1, 34, 1988). The regulation of longitudinal bone growth (LBG) is complex, as it includes among others nutritional and endocrine factors. However, very little is known about growth factors effects on LBG, as they are produced locally and act in a paracrine/autocrine manner. Immunohistochemical studies have identified TGF-β bound to the matrix of calcified cartilage and bone, and TGF-β has been found to be released into the culture medium by chondrocytes. We investigated the effect of recombinant human (rh) TGF-β2 (kindly provided by Ciba-Geigy, Basel, Switzerland) infusion on the changes induced by unloading in the cellular organization of the growth plate in rats. Hindlimb suspension for 14 days induced a 15% reduction in the growth cartilage length, mostly due to a 19% decrease in the proliferative zone length (371 ± 22.0 vs 435.5 ± 17.9 μm, unloaded vs control respectively, P<0.05). Systemic infusion of rhTGF-β2 at low dose (2μg/kg/day) in unloaded rats was found to induce a 9.5% increase in the proliferative zone length (399.7 ± 10.5 vs 371.7 ± 22.0μm, treated unloaded vs unloaded respectively, P<0.05) which reached values which were not significantly different in normal loaded animals. These results show that systemic administration of rhTGF-β2 stimulates the proliferation of chondrocytes, impaired in the epiphyseal growth plate of unloaded rats.