The sequence of proximal tubular damage and repair after gentamicin sulfate administration was studied by light and electron microscopy in Fischer 344 rats. The drug was administered at a dose of 40 mg/kg for up to 14 days. Although epithelial destruction was progressive with time, the extent and degree of tubular damage varied among animals at each interval. Tubule regeneration began to occur by the tenth day despite continued drug administration. Regenerating cells appeared to originate from residual epithelial cells in areas of tubular damage. The morphologically immature regenerating cells are apparently metabolically immature as well and appear not to be susceptible to toxic effects of the drug. Tubules were repopulated by 3 days following cessation of gentamicin administration. Except for foci of tubular atrophy and interstitial fibrosis, cortical tissues were comparable to controls ultrastructurally at the end of 31 days.