Intravascular injection of radionuclide-labeled microspheres was used to compare the blood supply to diethylnitrosamine-induced hyperplastic liver nodules and hepatomas with the blood supply to the surrounding, histologically normal liver. Microspheres injected into the heart or portal vein lodged in the organs of control and diethylnitrosamine-treated rats providing a quantitative index of blood supply to the microvascular bed. The blood supply is expressed as percentage of cardiac output (arterial) or cpm (portal) per organ, lobe, g tissue, etc. The fraction of the cardiac output received by lung, kidneys, spleen, and liver was similar in control and carcinogen-treated animals. The arterial blood supply of 23 nodules and hepatomas was variable [1.17 +/- 0.22% (S.E.) cardiac output per g, fixed weight], but it was similar to the arterial supply to the surrounding tissue (1.12 +/- 0.21% cardiac output per g, fixed weight). In contrast the portal blood supply to 25 selected lesions wa 39 +/- 6% that of the surrounding liver tissue. There was no apparent relationship between blood supply and lesion size or histological appearance. While only 0.13 +/- 0.04% of the microspheres injected via the portal system were recovered in the lungs of control rats, approximately 100 times this number bypassed or escaped the liver containing nodules and hepatomas and lodged in the lungs. Such alterations in blood flow could contribute to biological diversification of hepatic lesions in successive stages of cancer evolution and could facilitate metastasis from the liver.