Secondary mania is increasingly recognized clinically, and consists of acute exhibition of manic symptoms without past or family history of affective disorder. It has been reported with toxic and metabolic disturbances, primary and metastatic brain tumors, epilepsy, and cerebrovascular events. A multifactorial etiology has been suggested. We report two men, 52 and 56 years old, who developed grandiosity, sleeplessness, irritable mood, hyperactivity, and paranoid and religious delusions, with attempted violence in one case. Both had no premorbid psychiatric history and were healthy except for hypertension. One patient had a normal neurologic examination, and the other had mild left hemiparesis and hyperreflexia. EEGs, brainstem auditory-evoked responses, and median nerve somatosensory-evoked potentials were normal. Magnetic resonance studies demonstrated infarction of the ventral pons (on the right in the patient with left-sided signs and on the left in the patient with normal neurologic examination). The two patients responded to lithium carbonate and neuroleptics and have not had further psychiatric symptoms in 18 months of follow-up. These cases emphasize the relationship of late-onset mania with predisposing brain disease, and they suggest that brainstem disturbances can influence mood, sleep, libido, and thought.