To explore whether lithium exacerbates neuroleptic-induced extrapyramidal symptoms (EPS), the authors prospectively rated 10 patients on neuroleptics before and after the addition of lithium. EPS ratings increased steadily after the initiation of lithium and were significantly elevated compared with baseline. Individual items that increased significantly were: gait, shoulder shaking, elbow rigidity, and tremor. These findings indicate that usual therapeutic levels of lithium may significantly worsen neuroleptic-induced EPS. Potential mechanisms for this interaction are discussed.