Gonadotropin releasing-hormone (GnRH) regulates the hypothalamo-pituitary-gonadal axis in vertebrates. The regulation of GnRH is intimately related to information from the olfactory system. Additionally, GnRH neurons are thought to be derived from progenitor cells in medial olfactory placodes. The present experiments were conducted to characterize the earliest development of GnRH neurons in lamprey and to determine their relationship to cells and fibers derived from the olfactory system. Eggs from fertile adult sea lamprey were fertilized in the laboratory, and larvae were maintained for up to 100 days. GnRH neurons were visualized within the lamprey preoptic area and hypothalamus as soon as GnRH was detectable (22 days after fertilization). The number of neurons increased with age through day 100. GnRH neurons were never seen within the olfactory system. The cells and fibers of the olfactory system were identified using the lectin, Grifonia Simplicifolia-1 (GS-1). Overlap between the olfactory and GnRH systems were at the level of fiber projections. GS-1 reactive cells of apparent placodal origin did not enter the region of the preoptic area or hypothalamus that contained GnRH neurons. Recently divided cells were labeled with the thymidine analog, bromodeoxyuridine (BrdU). The positions of BrdU-labeled cells after different survival times suggest a predominant medial-lateral radial neuron migration with a small number in positions suggestive of migration between the olfactory epithelium and the telencephalic lobes. Regardless of survival time, these cells were always found close to their entry point into the brain, suggesting minimal rostral-caudal migration. Based on these results, we hypothesize that GnRH neurons in developing lamprey originate within proliferative zones of the diencephalon and not in the olfactory system. Based on the overlap of olfactory- and GnRH-containing fibers from prolarval stages to metamorphosis, olfactory stimuli may play a major role in the regulation of GnRH secretion in lamprey.