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The monoclonal antibody RL23/36 has been shown to discriminate normal from malignant hepatocytes in man. In frozen sections of liver tissue from 25 Thai patients without hepatocellular carcinomas, the antibody reacted strongly and preferentially with hepatocytes. Reactivity with 7 hepatocellular carcinomas was invariably abnormal, being totally absent in 5 and partially lost in 2. This discrimination was superior to that achieved with Ca1 and 791T/36 monoclonal antibodies. In 2 cases of hepatocellular carcinoma, binding of RL23/36 to associated apparently non-malignant hepatocytes was abnormal, being absent in one and partially lost in the other. These data show that RL23/36 detects an antigenic determinant which is lost during malignant transformation of human hepatocytes, sometimes before the development of frank malignancy.