The immunohistochemical expression of retinoblastoma protein (Rb) and its phosphorylated form (pRb) was investigated in an in vivo sheep model, i.e., lung tissue exposed to asbestos-like fibers. Rb is a phosphoprotein with a central role in controlling the cell cycle, cell growth regulation, differentiation, and apoptosis. pRb functions as a checkpoint in the G(1) phase, favoring cell growth, while the hypophosphorylated form (Rb) not only promotes cell-cycle arrest and a return to the G(1) phase, but also appears to be a key player in most instances of apoptosis. pRb overexpression was detected in alveolar epithelium and the interstitium, especially close to the fluoro-edenite fibers, whereas Rb immunostaining was faint or absent. The data suggest that the altered balance between pRb and Rb expression may be a programmed response to protect the organism against uncontrolled cell proliferation.