For determination of the dose-response relationships of plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to the intranasal administration of gonadotropin-releasing hormone (GnRH), normal adult men were administered doses of 100, 200, 400, and 800 micrograms of GnRH on separate days, and plasma LH and FSH were measured before and after nasal insufflation of GnRH. Plasma LH was increased after a minimum dose of 200 micrograms GnRH. Median peak plasma LH levels occurred 30 minutes after intranasal GnRH and followed a log-dose relationship. When compared with intravenous GnRH, the biopotency of intranasal GnRH at the 200-, 400-, and 800-microgram doses was 1.1%, 2.3%, and 6.2%, respectively. Plasma FSH levels rose significantly only after the highest (800-micrograms) intranasal GnRH dose. From these data, we conclude that in eugonadal adult men the minimal effective dose of intranasal GnRH to elicit a significant pituitary (LH) response is 200 micrograms and that the relative efficacy of intranasal GnRH increases with the dose. In spite of the apparently low biopotency for intranasal GnRH, this route of administration may be considered as an alternative to the parenteral mode of GnRH delivery, and the lower biopotency can be partly overcome by increasing the dose.