The autoradiographic identification of chemically-induced, unscheduled DNA synthesis in primary cultures of adult rat hepatocytes is currently being validated as a predictive test for mutagens/carcinogens. Of 8 antihistaminic drugs tested, 2, pyrilamine maleate and tripelennamine HCl, were positive for unscheduled DNA synthesis. Further investigation of the mutagenic/carcinogenic potential of these compounds in alternate test systems is suggested.