Allopregnanolone is a known GABA(A) receptor agonist not previously given to men, or to women using oral contraceptives (OC). The effects of metabolites of sex hormones on the GABA(A) receptor are different between men and women. OC are known to change GABA(A) receptor subunit composition. These factors might play a role in the differential effect of allopregnanolone in men and women, and in women with or without OC. To study the sedative effect of and sensitivity to allopregnanolone in men and in women with OC, nine healthy men (mean age 24.6 years) and nine healthy women on OC (mean age 21.8 years) were given three, increasing, intravenous dosages (0.015, 0.03, and 0.045 mg/kg) of allopregnanolone. Saccadic eye velocity (SEV), subjective ratings, and electroencephalography (EEG) were used to evaluate the response to allopregnanolone. Repeated blood samples for analyses of serum allopregnanolone levels were drawn throughout the study day. Allopregnanolone decreased SEV more in women than in men, and increased subjective ratings of 'sedation'. The results in women on OC are similar to earlier results in women without OC. Subjective ratings of 'contentedness' decreased in men but increased in women. Serum levels of allopregnanolone were more highly increased in men compared to women. Other pharmacokinetic parameters were not different between sexes. On the EEG, beta power increased in men. In conclusion, men and women on OC reacted differently to allopregnanolone.