Characteristics of LH-RH interactions with the plasma membrane of the anterior pituitary were utilized to develop a radioligand- receptor assay for the hypothalamic decapeptide. Plasma membranes were prepared from rat adenohypophyses and association of 125I-LH-RH with the cell membrane was found to reach a plateau after 30 min incubation time. Sensitivity of the present competitive protein binding assay was 10 ng. The system was shown to be sensitive to structural changes in the LH-RH molecule. No cross-reactivity of (3--10) LH-RH, pyro-His-Trp-SerOMe and TRH was recorded with LH-RH, whereas slight cross-reaction was observed for (Lys8) LH-RH and (Ala4) LH-RH showed marked cross-reaction. Although the present system is not sensitive enough to estimate physiological levels of LH-RH it seems to be a valuable approach for setting up an LH-RH assay system.