Prominent sinusoidal dilatation of the liver, spleen, and adrenals has been observed in nude mice with transplanted human renal cell carcinoma (RCC). To confirm whether this is a paraneoplastic manifestations specific for patients with RCC, 145 human autopsy specimens of RCC, transitional cell carcinoma (TCC) and cerebral hemorrhage (CH) were studied histologically. Sinusoidal dilatation of the liver was found in nine of 45 RCC cases. That incidence rate was significantly high when compared with three of 50 TCC cases (P less than .05) and with none of 50 CH cases (P less than .005) in which sinusoidal dilatation of the liver was found. There were no significant differences among the RCC, TCC, and CH groups in the incidence of sinusoidal dilatation in the spleen and adrenals. The sinusoidal dilatation of the liver associated with RCC was unique in that it occurred focally in the mid-zone of the hepatic lobules without any findings related to passive congestion of the central vein, endothelial damage, or hepatocellular necrosis. This change was not necessarily accompanied by abnormal liver function, although sinusoidal dilatation has been reported as one of the histologic manifestations of the nonmetastatic liver dysfunction syndrome of RCC known as the Stauffer syndrome. Sinusoidal dilatation is thought to be one of the tumor-specific manifestations and the influence of some tumor products is suggested, although the exact etiology remains unclear.