We investigated the effects of age on adriamycin-induced nephropathy in mice. Disease was produced by a single intravenous injection of adriamycin (doxorubicin hydrochloride) (AD, 20 mg/kg) in female Balb/C mice of 5 and 12 weeks of age. Urinary protein and transforming growth factor (TGF)-beta1 concentrations were measured and the extent of glomerular sclerosis/hyalinosis and tubulointerstitial fibrosis was scored. Decorin and fibromodulin expression was quantified using reverse transcription-polymerase chain reaction. In normal mouse kidneys, urinary TGF-beta1 excretion and decorin and fibromodulin mRNA did not change with age. When nephropathy was induced, the 12-week-old group demonstrated significantly greater proteinuria, urinary TGF-beta1 excretion, and interstitial fibrosis ( P<0.05) than the 5-week-old group. Decorin and fibromodulin expression was not significantly different between the groups. We conclude that 12-week-old mice develop more severe nephropathy than the younger mice following administration of the equivalent weight-based dose of AD. Decorin and fibromodulin do not play a role in this difference.