Experiments were conducted to test the hypothesis that gonadotropin-releasing hormone immunoreactive (GnRH-ir) and FMRFamide-ir neurons present in the brain and nervus terminalis originate in the embryonic olfactory placode. The olfactory placodes were bilaterally extirpated in stage 26 or stage 29 embryos of the axolotl, Ambystoma mexicanum, which were then reared for 4-8 months before they were examined immunohistochemically. In experimental subjects with bilateral loss of olfactory epithelia, nerves and bulbs, there was complete absence of GnRH- and FMRFamide-ir neurons in the terminal nerve, and in septal and preoptic areas, and complete absence of large diameter peptidergic fibers associated with the TN-septo-preoptic system. However, GnRH-ir perikarya in the posterior tubercle, and FMRFamide-ir perikarya in the ventral hypothalamus, and small diameter peptidergic fibers were not affected by placodal ablation. These results support the hypothesis that contrary to recent reports, GnRH-ir neurons have more than one embryonic origin. Region-specific patterns of staining with antisera directed against different molecular forms of GnRH support the interpretation that GnRH-ir neurons of placodal origin express mammalian GnRH, whereas GnRH-ir neurons of non-placodal origin, in the posterior tubercle, express chicken GnRH II.