In this study, we assessed the profile of cell proliferation, Na,K-ATPase activity and apoptosis in primary cultures of proximal tubule cells. Freshly isolated proximal tubules exhibited apoptosis very early in culture: floated cells within 6 hr; attached tubule cells within 20 hr. The onset of apoptosis in either attached or floated proximal tubules was accompanied by a decline of Na,K-ATPase activity, indicating a close relationship between apoptosis and dedifferentiation. The ratio of apoptosis was highest at the lag phase and lowest at the rapid growth phase, reflecting an inverse relationship between mitogenesis and apoptosis. Our data indicate that apoptosis is involved in the growth and early downregulation of Na,K-ATPase activity in primary cultures of proximal tubule cells.