Ms. A had two similar episodes with clear evidence of mania and psychosis. During the first episode, she was taking both clarithromycin and prednisone; the mania and psychosis were thought to be due to the prednisone. Before the second episode, Ms. A was taking clarithromycin alone. We think that Ms. A’s case represents clarithromycin-induced mania. Her dose of clarithromycin in both episodes was 500 mg b.i.d. as opposed to the relatively high doses (1000 mg b.i.d.) described in the treatment of disseminated Mycobacterium avium-complex infections in two AIDS patients who developed manic episodes (1), similar to the results reported by Cone et al. (2). Clarithromycin has excellent CSF penetration (3), but no reports of possible interaction with central neurotransmitters were found in the literature, although such interaction is a plausible assumption. There have been several reports of CNS side effects of clarithromycin: dizziness, lightheadedness, confusion, and insomnia (4), as well as visual hallucinations (5).