The goal of this study was to investigate the behavioral and subjective effects of a single dose of progesterone in men and women. Certain metabolites of progesterone (e.g., allopregnanolone) are potent positive allosteric modulators of GABA(A) receptors, and produce sedative-like effects in laboratory animals. This study was designed to examine the acute effects of these neurosteroids in humans. Women (n=7) in their early follicular phase and men (n=10) received intramuscular injections of progesterone (200 mg) or placebo. Dependent measures included plasma levels of progesterone and allopregnanolone, self-report measures of mood and subjective effects and behavioral measures of psychomotor performance. Plasma concentrations of progesterone and allopregnanolone increased reliably and with little intersubject variability after drug administration, and levels were similar in men and women. Administration of progesterone produced small, delayed increases in heart rate and feelings of fatigue, and it impaired smooth eye pursuit. These results suggest that, although the effects are modest and not simply related to plasma concentrations, progesterone and its metabolites can produce sedative-like effects in both men and women.