Renal morphology was studied by light and electron microscopy in 10 patients after 25 mg/kg body weight of amphotericin B as part of a controlled study designed to evaluate the possible protective effects of mannitol against the nephrotoxicity of amphotericin B. Five patients received amphotericin B 1 mg/kg body weight every other day and five received amphotericin B and mannitol 1 g/kg body weight in the infusion. Small arterial and arteriolar changes were present in all biopsies and were characterized by focal vacuolization of medial smooth muscle cells. Electron microscopy suggested formation of these vacuoles by fusion of dilated endoplasmic reticulum. A few small vacuoles were also seen in renal biopsies of age matched patients who did not receive amphotericin B. Vacuoles in biopsies of the amphotericin treated patients were considerably larger (P less than 0.001) and much more numerous (P less than 0.001) than in controls. It is hypothesized that the vacuoles in the amphotericin B treated group represent the morphologic effect of intrarenal vasoconstriction caused by amphotericin B therapy. Nephrocalcinosis was observed in all biopsies and appeared to originate by precipitation of calcium salts in tubular casts.