Lethargy, marked muscle weakness and rigidity, a maximal temperature of 40 degrees C, and a maximal creatine kinase value of 17,240 IU/liter developed in a 36-year-old woman following treatment with several neuroleptics. Initial treatment with dantrolene was unsuccessful. The patient's condition improved gradually over a 10-day period with no specific therapy. Muscle biopsy revealed a contracture pattern diagnostic of malignant hyperthermia susceptibility, as well as abnormal sensitivity to fluphenazine. This report may be the first description of a patient with neuroleptic malignant syndrome in whom muscle biopsy response similar to that seen in malignant hyperthermia occurred and documents that dantrolene is not uniformly successful therapy for this syndrome.