Cognitive dysfunction in patients with schizophrenia is a strong correlate of poor outcome than any other symptom domain. To have greater knowledge about the effects of antipsychotics on cognitive function, subjects of this study were healthy volunteers who had no confounding variables typically found in patients with schizophrenia. The cognitive function of healthy volunteers in response to single doses of haloperidol, risperidone, aripiprazole, and amisulpride in a double-blind placebo-controlled trial was investigated. Assessments for the computerized neurocognitive test, mental and physical sedation, and extrapyramidal symptoms were performed within 1 week before (baseline) and approximately 4 hours after drug administration. Compared to the placebo, single administration of amisulpride at 400 mg in healthy volunteers enhanced word fluency test performance and remained intact after controlling for sedation and extrapyramidal symptoms. Significant improvement in some measurements of the computerized neurocognitive test was also observed in each antipsychotic-treated group but may have been related to practice effect. These findings suggest that amisulpride may have cognitive-enhancing effects in healthy volunteers.