We model the effect of gonadotropin-releasing hormone (GnRH) on the production of luteinizing hormone (LH) by the ovine pituitary. GnRH, released by the hypothalamus, stimulates the secretion of LH from the pituitary. If stimulus pulses are regular, LH response will follow a similar pattern. However, during application of GnRH at high frequencies or concentrations or with continuous application, the pituitary delivers a decreased release of LH (termed desensitization). The proposed mathematical model consists of a system of nonlinear differential equations and incorporates two possible mechanisms to account for this observed behavior: desensitized receptor and limited, available LH. Desensitization was provoked experimentally in vitro by using ovine pituitary cells in a perifusion system. The model was fit to resulting experimental data by using maximum-likelihood estimation. Consideration of smaller models revealed that the desensitized receptor is significant. Limited, available LH was significant in three of four chambers. Throughout, the proposed model was in excellent agreement with experimental data.