Objective: This study sought to determine whether patients with dementia with Lewy bodies (DLB) and psychosis responded to treatment with olanzapine. Methods: This was a post hoc analysis of a subgroup of patients with DLB included in a larger double-blind, placebo-controlled, randomized parallel group trial of olanzapine for the treatment of psychosis in patients with Alzheimer’s disease. Patients meeting the consensus criteria for DLB and exhibiting parkinsonism and visual hallucinations were selected from the initial study. Psychosis was assessed with the Neuropsychiatric Inventory/Nursing Home (NPI-NH) version and the Brief Psychiatric Rating Scale (BPRS). Extrapyramidal symptoms were evaluated with the Simpson-Angus scale. Results: Twenty-nine patients met the criteria for DLB; 10 were randomized to placebo, 5 received 5 mg of olanzapine, 7 received 10 mg of olanzapine and 7 received 15 mg of olanzapine. Patients with DLB treated with 5 mg of olanzapine showed significant reductions in delusions and hallucinations. Patients treated with 10 mg showed a significant reduction in the NPI-NH delusion subscale score. No significant differences were found between the 15-mg group and the placebo group. Confirmatory findings emerged from an analysis of the BPRS. Caregivers reported decreased disruptions in their occupational routines for the group receiving 5 or 10 mg of olanzapine. There was no significant exacerbation of parkinsonian symptoms in any study group, no decrement in Mini-Mental State Examination scores in any of the treatment groups, and symptoms suggestive of anticholinergic toxicity did not differ among treatment groups. Conclusions: This preliminary analysis suggests that olanzapine (5 or 10 mg) reduces psychosis in patients with DLB without worsening parkinsonism.