The present study was performed to determine if perospirone, a novel antipsychotic drug with D2/5-HT2A antagonist and partial 5-HT1A agonist properties, would improve memory organization in twelve patients with chronic schizophrenia. Switching to equivalent dose of perospirone from prior antipsychotic medication was associated with a significant improvement in indices of verbal memory organization of the Auditory Verbal Learning Test. Negative symptoms and extrapyramidal side effects were also ameliorated after switching to perospirone. The distinct cognitive enhancement profile of perospirone may be attributable to its partial 5-HT1A agonist action.