Adriamycin (ADR) induces glomerular damage in rats with persistent severe proteinuria which reaches a peak 15 days after a single 5 mg/kg intravenous (i.v.) injection. We studied in ADR-treated rats the effects of a low-protein (6%) diet (LPD) supplemented with keto acids on urinary protein and glycosaminoglycan (GAG) excretion and glomerular GAG contents. Animals were divided into three groups: group 1 was used as control, and groups 2 and 3 received a single i.v. injection of ADR; group 2 was fed a standard diet (21% protein) and group 3 an LPD. After ADR, group 2 developed heavy proteinuria and showed a progressive increase in urinary GAG excretion starting a few days after the beginning of proteinuria onset and persisting throughout the experiment. After ADR, group 3 (LPD treatment) did not develop proteinuria, and the level of urinary GAGs was comparable to that of controls. The glomerular GAG level in ADR-treated rats was greatly reduced as compared to controls; this decrease was partly eliminated in rats on an LPD. These results suggest that an LPD has a direct effect on cellular GAG production and turnover in ADR-induced glomerulonephritis.