The role of fluoride in aluminium neurotoxicity was studied using an in vitro system of cultured hippocampal neurons from foetal rats. Sodium fluoride (50 microM) and aluminium chloride (12.5 microM) were administered alone or in a specific combination (50 + 12.5 microM) in a 14-day culture in a chemically defined medium before staining of neurofilaments. Neuronal aggregates interconnected by neuritic fibers were detected light microscopically in control cultures. The aggregates and the fibers stained positive for neurofilament proteins. In cultures treated with aluminium chloride the development of the interconnecting fibers was affected, resulting in a fusion pattern of the aggregates. This phenomenon was enhanced when sodium fluoride was given together with aluminum chloride. It was concluded that aluminium interferes with the metabolism of the neuronal cytoskeleton and that this interference is potentiated by fluoride.