Research in hepatocellular gene therapy requires a consistently reproducible cell marker to detect transplanted hepatocytes. We have used a Y-specific genomic DNA probe to accomplish this goal. This technique enables the identification of transplanted male cells in recipient female tissues. Donor hepatocytes from male mice were transplanted into female mice via splenic injection. Recipient mouse livers were harvested 1, 24, and 48 hr after transplant. Transplanted (male) hepatocytes were detected in liver biopsy sections using in situ hybridization with the Y chromosome probe.