Premenstrual syndrome (PMS) depends on gonadal hormones produced by the corpus luteum. Given the facilitory actions on GABAergic inhibitory neurotransmission exerted by certain progesterone metabolites, further studies on the GABAA receptor system in premenstrual syndrome are warranted. This study evaluated the benzodiazepine sensitivity in PMS patients and control subjects, using saccadic eye velocity (SEV) and visual analogue ratings of sedation as dependent measures. PMS patients displayed a significantly reduced SEV responsiveness to benzodiazepines compared to control subjects in the follicular phase, whereas there was no difference between groups in the luteal phase. In the luteal phase, the sedation response to benzodiazepines was significantly reduced in PMS patients compared to control subjects. There was also an influence of PMS symptom severity on these measures, as high-severity PMS patients displayed blunted SEV and sedation responses to benzodiazepines compared to low-severity patients. These results indicate that PMS patients have a reduced functional sensitivity at the GABAA/benzodiazepine receptor complex throughout the menstrual cycle.