Introduction: It is assumed that female and male schizophrenic patients respond differentially to acute and chronic treatment with antipsychotics because of pharmacokinetic and pharmacodynamic factors linked to hormonal and constitutional gender differences. However, to date no empirical evidence exists in support of this notion. Methods: In a naturalistic clinical study, we investigated gender differences in a sample of schizophrenic inpatients with acute exacerbation treated with the atypical antipsychotic amisulpride, a selective dopamine D2/D3 receptor antagonist with proven antipsychotic efficacy. Prescribed amisulpride dose, plasma level, clinical response (CGI), and side effects (UKU) were assessed in 99 patients (62 % male, age 18-66 years) under antipsychotic monotherapy with amisulpride at daily doses ≥ 400 mg. Results: Female patients were significantly older (38.5 ± 11.8 years) than male patients (32.3 ± 10.9 years; P = 0.01). Prescribed amisulpride doses were comparable for men (673 ± 216 mg) and women (665 ± 229 mg). However, dose-corrected steady-state amisulpride plasma levels (men 0.41 ± 0.31 ng/mL/mg; women 0.60 ± 0.39 ng/mL/mg; P = 0.007) were significantly higher in female patients even after age adjustment. No significant differences between men and women emerged with respect to clinical response (77 % vs. 79 %, respectively) and the occurrence of any side effect (41 % vs. 37 %, respectively). Discussion: Except for higher dose-related plasma amisulpride levels in women, the explorative study unveiled no clinically relevant gender-specific aspects regarding prescribed dose, effectiveness, and side effects.