A deregulation in the peripheral and brain concentrations of neuroactive steroids has been found in certain pathological conditions characterized by emotional or affective disturbances, including major depression and anxiety disorders. In this article we summarize data pertaining to the modulatory effects of oral contraceptive treatment on neuroactive steroids in women and rats. Given that the neuroactive steroids concentrations are reduced by oral contraceptives, together with the evidence that a subset of women taking oral contraceptives experience negative mood symptoms, we propose the use of this pharmacological treatment as a putative model to study the role of neuroactive steroids in the etiopathology of mood disorders. Moreover, since neuroactive steroids are potent modulators of GABA(A) receptor function and plasticity, the treatment with oral contraceptives might also represent a useful experimental model to further investigate the physiological role of these steroids in the modulation of GABAergic transmission.