Saturated branched-chain aliphatic hydrocarbons, found in motor fuels, induce nephrotoxicity in male rats. Treatment of male rats with unleaded gasoline (0.04-2.0 ml/kg body wt, po) for 9 days increased markedly the number and size of hyaline (protein resorption) droplets in epithelial cells of the renal proximal convoluted tubules (PCT) and enhanced cellular exfoliation at high dose levels. No other treatment-related pathological effects were observed in the glomeruli, distal tubules, or medulla. The renal content of alpha 2u-globulin, a major urinary protein of male rats, was increased maximally by about 4.4-fold after gasoline administration (1.0 ml/kg, po, 9 days); no further increase was observed at higher doses. Immunoperoxidase staining of kidney tissue sections for alpha 2u-globulin revealed large accumulations of antigen localized in many of the PCT epithelial cells which contained hyaline droplets. The hepatic content of alpha 2u-globulin and its mRNA were not altered by gasoline administration. These data show, for the first time, that alpha 2u-globulin is accumulated in the kidneys of gasoline-intoxicated male rats and sequestered specifically in some of the hyaline droplets characteristic of gasoline-induced nephropathy. A hydrocarbon-induced defect in the renal lysosomal degradation of low-molecular-weight urinary proteins, rather than increased synthesis of these proteins, appears to cause hyaline droplet accumulation.