Sexual side-effects along with antipsychotic treatment may be linked to hyperprolactinemia and dopamine D ₂ receptor blockade. High prevalence of sexual dysfunction in un-medicated patients challenges the notion of sexual dysfunction as merely a side-effect of antipsychotic medication. Sexual dysfunction was assessed in fifty-six initially antipsychotic-naïve patients with schizophrenia using the UKU (Udvalget for Kliniske Undersøgelser) questionnaire. Serum-prolactin was obtained before and after six weeks of D _2/3 receptor blockade with amisulpride. At baseline 68% of patients reported one or more items of sexual dysfunction (males > females,), but the cumulative load of sexual dysfunction was similar in males and females. After 6 weeks treatment with amisulpride (mean dose 279 mg/day), 65% of patients reported one or more items of sexual dysfunctions (females > males). There was a significant sex*time interaction on mean sexual dysfunction load. All patients developed hyperprolactinaemia, and a significant effect of time and sex was found on s-prolactin (females > males). The results support that patients with schizophrenia report high levels of sexual dysfunction before antipsychotic exposure. After treatment, sexual side-effects were more frequent in females, coinciding with pronounced serum-prolactin increases. These findings suggest sex differences in sexual dysfunction before and after antipsychotic treatment.