We report on the successful treatment of two female patients with psychotic depression with the new atypical neuroleptic drug olanzapine. A 75-year-old female inpatient suffering from recurrent endogenous depression with tactile hallucinations and coenesthesia was refractory to a systematic sequential antidepressant treatment strategy during a 39-week period. After addition of the new atypical neuroleptic olanzapine to the SSRI citalopram, she showed immediate and ongoing symptom relief. In the second case of a 57-year-old female inpatient suffering from delusional depression, we observed marked symptom relief and correction of the delusions of impoverishment. Olanzapine is discussed with regard to its receptor-binding profile (antagonism to 5-HT2A- and D1-D4 receptors) as a potential neuroleptic drug in the treatment of affective disorders with psychotic symptoms.