This open-label pilot study explored the antiemetic activity of olanzapine, an atypical antipsychotic, in patients with advanced cancer requiring opioid analgesics for pain. Fifteen patients received 2 days of a washout and placebo "run-in" followed by two day periods on each of three doses of olanzapine (2.5 mgs, 5 mgs, and 10 mgs). Patients completed a daily food journal as well as the Mini Mental State Exam, Simpson Angus Scale, Barnes Akathisia Scale, and the Functional Assessment of Cancer Therapy-General across four time periods, with special attention being placed on the nausea item. Eleven women and 4 men with varied primary cancer sites participated. The average age of the sample was 58 years (SD = 16.8). All three dose levels were associated with significant reductions in nausea compared to baseline. Diary entries recorded by the subjects suggested substantial benefits to overall well being and the 5mg condition was associated with statistically significant improvement in overall quality of life over baseline (F = 12.0, p < 0.005). No extrapyramidal symptoms were noted and mental status exams were not changed over the course of the eight days. These results suggest an antiemetic effect for olanzapine and indicate the need for a controlled trial.