Postnephrectomy serum has been proved to enhance proliferation of mesangial cells in culture. Studies in offspring to uninephrectomized (UNx) mothers indicate that it remains active for a long period following UNx. On the other hand, postnephrectomy renal compensatory growth in vivo is known to be completed within a short period. In this study we assessed the proliferative responses of mesangial cells from single kidneys of rats which were cultured 48 h or 4 months following contralateral nephrectomy. The proliferative stimulus was provided by different postnephrectomy sera. Proliferation of both experimental cell populations was significantly greater than that of controls. Moreover, the proliferation rate of early postcontralateral nephrectomy mesangial cells was greater than those harvested 4 months after nephrectomy. We, therefore, propose that the early in vivo completion of single kidney compensatory hypertrophy, at least in part, is due to progressive blunting of renal cell responsiveness to the mitotic stimulus of the animal’s serum.