Concentrations of alpha and beta-subunits of S100 protein (S100-alpha and S100-beta) in rat kidney neoplasms, including renal cell and mesenchymal tumors, were determined using a highly sensitive enzyme immunoassay, and both types immunohistochemically localized in tissue sections. Concentrations of S100-alpha in each histological type of rat tumor were lower than in normal kidney, whereas levels of S100-beta (mean +/- SE: 29.7 +/- 14.2 ng/mg protein, n = 15) in renal cell tumors were significantly higher than in normal kidneys (0.55 +/- 0.06 ng/mg protein, n = 7), or mesenchymal tumors (1.21 +/- 0.43 ng/mg protein, n = 9). In normal rat kidney tissues S100-alpha was immunohistochemically positive in epithelial cells of the distal tubules, the thin limbs of loops of Henle, and the collecting ducts. No appreciable immunostaining for S100-beta was found in any nephron segment. Both S100-alpha and S100-beta were positive for renal cell tumors, indicating new appearance of the latter during renal carcinogenesis in rats.