Four antihistaminic drugs similar in structure to the rat liver carcinogen methapyrilene were administered to comparable groups of male and female F344 rats in their drinking water for most of their lifetime (80-108 weeks). The concentrations were 0.1% or 0.05% and the total doses received by the animals were comparable with that of methapyrilene which induced 100% incidence of liver neoplasms. No increase in incidence of liver neoplasms was observed after treatment with any of the four compounds, thenyldiamine, chlorothen, methafurylene, or methaphenilene, although each differed structurally from methapyrilene only in one atom or one position of substitution. There were a few animals with neoplasms not usually found in untreated F344 rats, but none of these was found in statistically significant numbers. These results suggest that none of the four analogs of methapyrilene was carcinogenic under the conditions of this study, and that the property of inducing liver neoplasms in rats was confined to the intact methapyrilene molecule.