This study investigated the mechanism of non-specific toxicity of non-reactive volatile organic compounds by using data reported in the literature. Inhalation toxicity data, in terms of LC50 for alcohols and alkanes in rodents, were examined in relation to their partitioning behaviour in the biological system. Regression analysis of the data showed that, after the elimination of the kinetic influence in the absorption process, lethal toxicity increases linearly with the octanol–air partition coefficient in a homologous series. Comparing this relationship with that for anaesthesia, it could be concluded that lethal toxicity of the test chemical series probably acts on the lipid bilayer plasma membrane through a non-specific biophysical mechanism similar to anaesthesia. The critical concentration hypothesis appears to be valid for lethal toxicity of the test series. It was also shown that toxicity data for the test series by other routes, namely oral, intraperitoneal and intravenous, give a similar toxicity–partition relationship to that by inhalation.