Cerebellar neurons in primary culture were exposed to methylmercury, a well-established neurotoxicant known as a cause of Minamata disease, at 0.1-1.0 microM for up to 72 hours and compared with the neurons undergoing apoptosis induced by withdrawing K+ from the medium. Cerebellar neurons treated with methylmercury at up to 0.3 microM showed morphological changes characteristic to apoptosis, depending on methylmercury dose; formation of apoptotic vesicles, disappearance of neurites and condensation of nuclear chromatin. In addition, soluble DNA prepared from the methylmercury-treated cells exhibited the typical DNA fragmentation pattern similar to that in cells undergoing apoptosis induced by K+ withdrawal. At higher concentration of methylmercury, however, a non-apoptotic pathway of cell death started to predominate over the apoptotic pathway. These results indicate that the death of cerebellar granule neurons induced by methylmercury is, at least at lower doses, apoptotic.