Eleven patients with systemic mycotic infections were treated with amphotericin B, 1 mg/kg, on alternate days. Five patients also received mannitol (M), 1 g/kg, in the amphotericin infusion, while six served as controls (C). Renal function studies prior to therapy were repeated at a total cumulative amphotericin B dosage of 25 mg/kg; renal biopsies were obtained from 10 patients. Inulin and creatinine clearances decreased in both the C and M groups, significantly so in the latter. Urinary concentrating ability of five patients (2C, 3M) decreased as did the capacity of three (1C, 2M) to acidify urine after an acid load. Neither the peak and valley levels of amphotericin B in serum nor the urinary excretion thereof differed between the C and M groups. Striking vacuolization of smooth muscle cells, previously unrecognized, was observed in the media of arterioles and arteries in all renal biopsies. Tubular calcification was present in both groups. In summary, M therapy (1 g/kg) did not protect against the nephrotoxicity of amphotericin B. A unique lesion of the renal vasculature secondary to amphotericin B is described.