Kallmann syndrome is a human genetic disorder characterized by the association of hypogonadism with the inability to smell, and is due to defects in the olfactory system development (i.e. incomplete migration of olfactory axons and of gonadotropin-releasing hormone producing neurons from the olfactory epithelium to the forebrain; aplasia or hypoplasia of olfactory bulbs and tracts). The human X-linked Kallmann syndrome gene and its chicken homologue have been cloned. Their protein products contain fibronectin type III repeats and a 'four-disulfide-core' domain also found in molecules that are involved in neural development. Consistent with the human phenotype, the chicken Kallmann gene is expressed in the developing olfactory bulb. At present the molecular and cellular mechanism of action of the Kallmann syndrome gene product is unknown. Based on expression studies and the characteristics domains of the predicted protein, it is hypothesized that the protein may be involved in targeting olfactory axons to the bulb. Alternatively, the Kallmann protein could be an extracellular matrix component required for the proper formation of the multilayered structure of the olfactory bulb.