The olfactory epithelium (OE) is unique in the mammalian nervous system as a site of continual neurogenesis. Though many studies have described this process in vivo and olfactory neurogenesis can be demonstrated in vitro, the specific factors that modulate this process have not been defined. Noting the common ectodermal origin and structural similarity between the OE and epidermis, peptide factors known to modulate epidermal differentiation were tested in OE cultures. Our results demonstrate that EGF acts as a mitogen for the basal cells that give rise to olfactory neurons and that transforming growth factor-beta s (TGF-beta s) promote neurogenesis. Using a neutralizing antibody, we show that it is likely that the endogenous neurogenic factor is TGF-beta 2, or a very closely related factor.