The forestomach carcinogenicity of butylated hydroxyanisole (BHA) was compared in males of the F344, SHR, Lewis and Sprague Dawley rat strains. Groups of 30 6-wk-old animals were given a pellet diet containing 2% BHA for 104 wk. Forestomach squamous cell papillomas and hyperplasias developed in all rats given BHA, independent of the strain, but the incidences of squamous cell carcinomas (SCCs) differed considerably: F344, 26.7% (8/30) SHR, 76.7% (23/30) SD, 36.7% (1130) Lewis, 6.7% (2/30). Cytotoxic effects, reflected by inflammation, were also most severe in the SHR strain, correlating well with the development of SCCs. The present results indicate that major strain differences exist regarding BHA rat forestomach carcinogenesis and that sensitivity to cytotoxicity might be an important parameter.