BACKGROUND: In a study initially designed to evaluate the specific protein gene product 9.5 expression in parietal epithelial cells of Bowman's capsule, a marked positivity was also observed in the tubular and collecting duct epithelial cells. Since protein gene product 9.5 is an important enzyme in the ubiquitin system of proteolysis, and plays a regulatory role in cell cycle and proliferation, its presence in specific segments of the nephron was of considerable interest. METHODS: We investigated protein gene product 9.5 and ubiquitin expression in both normal and pathologic renal samples (more than 100 cases) using an immunohistochemical technique. RESULTS: We found that protein gene product 9.5 and ubiquitin were constantly present in Bowman's capsule parietal cells and tubular/collecting duct epithelial cells, with the strongest positivity in metabolically active and proliferative conditions, such as tubular hypertrophy, cellular regeneration and crescent formation. Conversely, the expression of these molecules was attenuated in atrophic tubules. Podocytes were negative. CONCLUSION: The diffuse presence of the protein gene product 9.5 and ubiquitin in normal and pathologic metabolically active epithelial cells of the nephron suggests that these proteins (and likely the whole ubiquitin-proteasome complex) play a fundamental role in the mechanism upregulating protein metabolism of the kidney and that its expression is correlated with activated cellular functions, like proliferation.