The combination of lithium carbonate and neuroleptic is frequently used in the treatment of bipolar disorders. Four patients exhibited permanent neurological sequelae including cerebellar, pyramidal and extra-pyramidal signs after a long-term therapy with this association. Fever, stupor and pulmonary event were initially present. Neuropathological findings in one case only showed selective degeneration of cerebellar Purkinje cells, also noted as a characteristic feature in heat stroke and malignant hyperthermia. Lithium carbonate may be the main factor of neurotoxicity but hyperthermic states are probably involved in determinating brain damage, particularly cerebellar lesions.