The effect of OCS [oral contraceptive steroids] on the disposition and elimination of caffeine was examined. Caffeine (250 mg) was administered orally to 13 healthy males, 9 healthy females taking no OCS, and 9 healthy females on OCS. The t 1/2(.beta.) [elimination half-life] was significantly prolonged in women on OCS (10.7 .+-. 3.0 hr vs. 6.2 .+-. 1.6) (P < 0.001) as compared to women taking no OCS. Women on OCS had a significantly lower total plasma clearance (0.79 .+-. 0.21 ml/min per kg vs. 1.3 .+-. 0.35) and free clearance (1.12 .+-. 0.28 ml/min per kg vs. 1.97 .+-. 0.57) than women not taking OCS. Volumes of distribution and plasma binding were similar in both groups of females. When women taking no OCS were compared with men, all pharmacokinetic parameters were similar except for volume of distribution, which was significantly larger in the women (P < 0.05). OCS evidently impair the elimination of caffeine.