Cetrorelix (CET) is a potent luteinizing hormone-releasing hormone (LH-RH) antagonist and is used to prevent premature ovulation in IVF (in vitro fertilization) procedures. The objective of the present study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the LH suppression and LH surge delay after single doses (SD) and multiple doses (MD) of CET in healthy premenopausal women without ovarian stimulation. CET was given by subcutaneous route (SD, 0.25, 0.5, or 1 mg) on cycle day 3 and as similar multiple once-a-day doses from cycle day 3 to day 16 in two consecutive menstrual cycles. The concentration-time data of CET and LH were used for PK/PD modeling. A two-compartment model described the PK of CET with median terminal half-life estimates of 9.2 and 54.5 hours after SD and MD, respectively. An indirect-response Emax model was used to describe the LH suppression and the LH surge delay. LH suppression was linked to plasma concentrations of CET, while the delay in the LH surge was linked to the PK of CET through a hypothetical effect compartment. Since the SD regimen on day 3 did not cause significant delay, these values were used as controls in the analysis of surge delay in MD data. The IC50 (for suppression) estimate was 0.73 ng/ml for SD, and EC50 (surge delay) was 1.42 ng/ml for MD. The PK/PD model adequately described the LH suppression and the surge delay.