The serum concentrations of 3-keto-desogestrel (KDG) have been determined radioimmunologically in 11 female volunteers on Day 1, 10, and 21 of the 1st, 3rd, 6th, and 12th cycle of treatment with 30 micrograms ethinylestradiol and 150 micrograms desogestrel during the first 4 hours and 24 hours after intake. On the first day of each cycle the KDG levels were low, but increased thereafter until Day 21. Highest serum concentrations were measured on Day 21 of the 3rd and 6th cycle with peak levels between 1.5 and 6.2 ng/ml. Contrary to this, the KDG levels were significantly reduced during the 12th treatment cycle. The serum concentrations of SHBG rose significantly between Day 1 and Day 21 of each cycle reaching values which were 3-fold of those at the beginning of treatment. During the pill-free intervals, SHBG levels decreased but remained elevated as compared to controls. There was a significant correlation between the SHBG levels and the area under the KDG-concentration-versus-time curves (AUC) indicating a pronounced influence of the serum steroid-binding protein upon the pharmacokinetics of KDG. There were great interindividual differences in the KDG levels. The serum levels of the individual woman remain, however, in a relatively constant range throughout the treatment period of 12 months, possibly due to genetic factors.