A mechanism for rapid death in cocaine abusers is proposed based on the neuroleptic malignant syndrome (NMS). The mechanism involves decreased postsynaptic availability of dopamine either through direct receptor blockade, as postulated in classical NMS, or through relative dopamine depletion, as postulated in cocaine withdrawal. The hallmark symptoms of NMS include hyperpyrexia and muscular rigidity, but the cocaine associated syndrome is atypical in having minimal rigidity. This lack of muscle rigidity, however, appears to be consistent with NMS-like syndromes accompanying other conditions involving dopamine depletion rather than blockade. Treatment implications are that dopamine antagonists, which are usually prescribed for cocaine overdose, may be contraindicated and instead, dopamine agonists may reverse this rapidly fatal syndrome.