Four benzodiazepine tranquillizers were tested for their ability to initiate or promote the development of preneoplastic and neoplastic rat liver lesions. In comparison with the liver carcinogen, N-2-fluorenylacetamide, the benzodiazepines exhibited no initiating activity during a 14-week period of daily administration by gavage. To study the promoting activity, N-2-fluorenylacetamide was used to initiate altered foci and neoplastic nodules in rat liver during 8 weeks and then the benzodiazepines were administered by daily gavage for a period of 12 weeks. The liver tumor promoter phenobarbital had a substantial enhancing effect upon the persistence of nodules but none of the benzodiazepines showed a similar effect. Thus, in the process model systems used, to detect initiating or promoting potential effect, the benzodiazepine tranquillizers failed to exhibit either an initiating or a promoting action.