The reduced progesterone metabolite tetrahydroprogesterone is a potent positive modulator of GABA(A) chloride conductance that exerts powerful neuroinhibitiory and anti-seizure effects in animal models. Cyclic natural progesterone use may lessen seizure frequency in women with catamenial seizure exacerbation. We report a case in which efficacy was eliminated during concomitant treatment with a reductase inhibitor. The observation suggests that a reduced metabolite, rather than progesterone itself, was responsible for improved seizure control.