Objective and Methods: Reduction of kidney tissue results in a hypertrophy of the remaining intact nephrons. The mechanisms controlling this compensatory renal hypertrophy are not clearly defined. According to the "workload hypothesis" an initial increase in glomerular filtration rate results in an elevation of tubular flow that eventually induces hypertrophy of proximal tubules. In order to test for this hypothesis, tubular cells (LLC-PK1 and mouse primary proximal tubular cells) were grown to confluence and, subsequently, superfused for 24 hours with serum- and hormone-free medium. Results: Superfusion of proximal tubular cells at flow velocities up to 1 mm/s resulted in gradual increases of cellular protein content without changes in DNA concentration. Accordingly, the protein/DNA ratio, as a measure of cellular hypertrophy, was 40% higher in superfused cells compared to unsuperfused control cells. These changes were paralleled by significant increases in cell size. Interestingly, conditioned medium taken from superfused but not from unsuperfused cells induced significant hypertrophy and cell growth of control cells. Degradation of ATP by apyrase (7.5 U/ml) did not attenuate flow-induced cell hypertrophy, while it was significantly reduced by the mTOR inhibitor rapamycin (20nM/l). Conclusion: These results demonstrate that cell growth of proximal tubular cells is regulated by flow. Moreover, the data are compatible with the hypothesis that compensatory hypertrophy of proximal tubules is induced by an initial increase in GFR and tubular flow. The mechanisms connecting flow and cell growth appear to be independent of extracellular ATP while they include the mTOR pathway.