Background Higher levels of circulating oestrogens in women and testosterone in men have been shown to have a protective effect against the clinical manifestations of schizophrenia, mostly with respect to negative symptomatology. Certain studies suggest that they also have a protective effect against the neuropsychological impairment observed in the disease. We investigated whether greater prenatal exposure to estrogens in women and to testosterone in men, reflected by the 2D:4D ratio, was similarly associated with decreased negative symptomatology and improved neuropsychological functioning in patients. Method 51 schizophrenia patients and 50 healthy participants were administered a neuropsychological battery. The 2D:4D ratio was measured in all participants. Positive, negative, and affective symptoms were assessed in patients. Regression analyses were conducted separately in male and female subgroups. Results No associations with positive symptoms were revealed. In male patients, the 2D:4D ratio was positively associated with avolition and inversely associated with anxiety. In female patients, it was inversely associated with alogia, and tended to be positively associated with depression. No association between higher prenatal concentration of the relevant sex hormone and improved neuropsychological performance emerged in patients. Conclusions Higher concentrations of prenatal testosterone in male patients, and prenatal oestrogens in female patients, are associated with a decrement in certain aspects of negative symptomatology. In addition, prenatal sex hormone concentration seems to be associated with predisposition to anxiety in male patients, and to depression in female patients.