Acute lethal toxicity (the negative logarithm of molar concentrations of 12 h acute median lethal, expressed as 12 h-log1/LC50) of 46 benzene derivatives to Rana japonica tadpoles was determined. 1-octanol/water partition coefficient (logKow)-dependent models were developed to study the toxicity of different categories chemicals. In an effort to model all chemicals, response surface analyses and stepwise multiple regression analyses were performed and successful models were obtained. A general and robust QSAR model was achieved with the combined application of variables reflecting hydrophobicity, electric property, and molecular size respectively (12h-log1/LC50 = 0.393logKow - 0.428Elumo + 0.0110Vol. + 1.362 n = 51, r2 = 0.834) using stepwise multiple regression analyses. Because of strong dissociation of carboxyl group greatly decreasing their observed toxicity, using logDow in instead of logKow the quality of the models is greatly improved. The conventional r2 and cross-validation r2(CV) were 0.914 and 0.785, respectively, indicating that QSAR was both internally consistent and highly predictive.