To provide pharmacokinetic data for a safety evaluation of long-term use of the monthly injectable Cyclofem (25 mg of medroxyprogesterone acetate (MPA) and 5 mg of estradiol cypionate), 9 fertile Chinese women 27-34 years of age were enrolled in a 12-month clinical study. Serum samples were collected immediately prior to drug administration and on days 1, 3, 5, 7, 14, 21, and 28 after monthly injection. After injections 1, 6, and 12, maximum serum MPA concentrations were observed on days 3.4 +or- 0.9, 4.3 +or- 2.2, and 3.7 +or- 2.6, respectively. Maximum concentrations of serum MPA during treatment cycles 1, 6, and 12 were 3.75 +or- 1.27, 5.54 +or- 1.79, and 5.55 +or- 1.80 nmol/l, respectively, while the corresponding areas under the curve were 55.84 +or- 28.15, 95.45 +or- 26.56, and 98.81 +or- 21.84 nmol/l per day. There was significant interindividual variation in the pharmacokinetics of MPA after intramuscular injection. No significant change was recorded in mean MPA residence time after single and multiple injection. Noted was a trend of increases in MPA maximum serum concentration and areas under the curve during the first 6 months of treatment, followed by no further enhancement in the last 6 months. Peak estradiol levels were within the normal range of the preovulatory phase. These findings suggest that long-term Cyclofem use is not associated with drug accumulation. As a safe, highly effective formulation, Cyclofem offers women around the world yet another contraceptive choice.