The antihistaminic agent methapyrilene hydrochloride (MPH, CAS No. 135-23-9) has been reported as a potent rat hepatocarcinogen. However, neither the action mechanism nor mutagenicity of MPH have been clearly elucidated yet. Chromosomal aberration (CA) tests were performed with MPH in CHO-K1-BH4 and CHL cells without a metabolic activation system. Isochromatid break-like aberrations were observed in metaphases of CHO-K1-BH4 cells treated with MPH. MPH induced CA more effectively at higher pH in equitoxicity base. In contrast to CHO-K1-BH4 cells, typical chromatid type exchanges were observed in CHL cells treated with MPH. These results clearly support the results of other researchers that MPH induce chromosomal aberration and imply that MPH induces cancer in animal via other mechanisms than mere DNA damage or gene mutation which had been nearly proven to be negative by many researchers. It was suggested that pH variation might increase the sensitivity of CA tests for certain category of chemicals with dissociation potential.