Gender differences in schizophrenia include a later disease onset and second peri-menopausal peak in women, and evidence that psychopathology varies according to the menstrual cycle phase. Possible mechanisms for these gender differences include hypotheses based on animal studies demonstrating that estrogen increases striatal dopamine D2 receptors. We retrospectively investigated the relationship between gender and striatal dopamine in humans using SPECT imaging and the post-synaptic D2 radioligand epidepride. A total of 15 males (mean age = 35.0 ± 7.5 yrs) and 7 females (mean age = 32.3 ± 6.4 yrs) were evaluated from a database consisting of 10 healthy controls (7 males, 3 females), and 12 patients with social phobia (8 males, and 4 females). Multivariate analysis was performed using input variables of gender, group (control vs. social phobia), time of imaging; and an output variable of D2 receptor density (striatal to frontal cortex ratio). Findings revealed that, independent of being a patient or control, females had significantly higher values than males in all measures of striatal D2 receptor density (p = 0.0014). Furthermore, greater variability in D2 receptor density was observed in females compared to males. Consequently, post-synaptic D2 receptor density appears to be highly dependent on gender, and this should be taken into account in future studies of striatal dopamine. Increased striatal D2 receptor density in females may be secondary to the effects of estrogen, while increased D2 receptor variability may reflect estrogen changes over the menstrual cycle. These results suggest possible mechanisms for gender differences in psychiatric disorders like schizophrenia.