Primary cultures of human thyroid cells prepared from fragments discarded during the course of prescribed surgery were examined for their sensitivity to the DNA-damaging activity of selected chemicals in order to assess if they can represent a reliable model for genotoxicity studies. DNA fragmentation was measured by the alkaline elution technique. Positive dose-related responses in the range of subtoxic concentrations were obtained after 1 hr of exposure to the direct-acting alkylating agents N-nitroso-N-methylurea (0.3-3 mm), N-nitroso-Nethylurea (1-10 mm), methyl methanesulphonate (0.1-1 mm) and ethyl methanesulphonate (1-10 mm). In contrast, any meaningful evidence of DNA fragmentation was absent in cultures exposed for 20 hr to N-nitrosodimethylamine (1-100 mm) and N-nitrosodiethylamine (10-100 mm). This suggests that in human thyroid cells the level of mixed-function oxidase activity is not sufficient to give rise to effective concentrations of the reactive species of the latter two procarcinogens.