Implanon is a long-acting reversible contraceptive method, consisting of a single rod that is applied subdermally. Ovulation inhibition was determined by serum progesterone (P) levels and ultrasound scanning (USS) of the ovaries. Ovarian function was further assessed by serum estradiol (E2) levels. The effects of Implanon on serum gonadotropin levels (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) and on cervical mucus were also investigated, by means of Insler scores and sperm penetration tests. The effect of the endometrium was assessed by endometrial biopsies and USS. The Pearl index was calculated over 13 studies performed according to Good Clinical Practice (GCP), including 1716 women using Implanon. Return of ovulation after implant removal was determined by P levels and USS of the ovaries. The contraceptive efficacy of Implanon was high, with zero pregnancies during 53,530 cycles (4103 woman-years), resulting in a Pearl index of 0.0 (95% confidence interval, 0.00-0.09). This was achieved by inhibition of ovulation, which was reflected by suppressed P levels, as the primary mode of action. Ovulation was inhibited, but otherwise ovarian activity was still present (follicle growth, E2 synthesis). The FSH serum concentrations were only slightly lower than preinsertion levels and LH surges were prevented. The viscosity of the cervical mucus was increased. The endometrium was thin but not atrophic; it showed primarily inactive or weak proliferation. Return of ovulation after removal of Implanon was rapid.