PIP: Serum norethindrone (NET), estradiol-17 beta (E), progesterone (P), and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were radioimmunoassayed in 15 women after injection of 300 mg norethindrone enanthate (NET-EN) in 2 ml of oil (5 women), 200 mg NET-EN in 2 ml of oil (5 women), and 200 mg NET-EN in 1 ml of oil (5 women). These values were measured twice a week for 4-6 months to determine 1) the effect of various serum NET concentrations upon hypothalamic/pituitary-ovarian function; 2) intersubject variability of this effect; 3) between-subject variability of serum NET values; 4) the effect of an increase in NET-EN dosage or in the volume of the vehicle; and 5) the correlation between uterine bleeding and serum NET, E and P patterns. Peak serum NET levels were reached 4-15 days (median 7 days) postinjection. These high levels lasted about 20 days postinjection and then decreased, quickly at first and then gradually. Serum NET averaged 1.0 and .38 ng/ml 60 and 120 days postinjection and continued to be measurable in some of the subjects for up to a year. Calculations of day levels of serum NET revealed 63% in the 1st 20 days, 26% in the 2nd, and 11% in the 3rd. Follicle development occurred between 33-116 days postinjection (median 43 days) and was followed by ovulation in only 1 subject (45 days postinjection) with the 2nd earliest ovulation at 80 days postinjection. Uterine bleeding patterns were independent of dosage of NET-EN. The higher dose of NET-EN provides no contraceptive advantage, and the larger vehicle has no effect. A variability of positive feedback inhibition among subjects is thought to be responsible for differing patterns of return to ovulation, suggesting that for contraceptive purposes a regimen of 150 mg or less NET-EN every 6 weeks may be appropriate.