During the early stages of auditory development, the inner ear (otocyst) releases an unidentified, diffusible factor that promotes neurite outgrowth from the associated statoacoustic ganglia (SAG). Using a variety of criteria, the present study compared the neurite- and survival-promoting properties of this otocyst-derived factor (ODF) to the neurotrophins NGF, BDNF, NT-3, and NT-4 and ciliary neurotrophic factor (CNTF). Ganglia known to respond to specific growth factors were cultured in the presence of ODF. ODF failed to promote neurite outgrowth from trigeminal, ciliary, sympathetic, or dorsal root ganglia, suggesting that ODF may have properties different from other identified growth factors. In complementary experiments, SAG explants were cultured in ODF, the neurotrophins, and CNTF. The extent of outgrowth was greatest in the presence of ODF and CNTF, with the neurotrophins having little effect. In neuron-enriched, dissociated cell cultures, ODF promoted both survival and outgrowth of SAG neurons. However, neither the neurotrophins nor CNTF, alone or in combination, promoted the survival or outgrowth of dissociated SAG neurons. Thus, the outgrowth seen in the explant cultures appears to be due to indirect effects via the ganglionic nonneuronal cells. The addition of anti-NGF antisera failed to block the activity of chick, rat, or mouse ODF, further indicating that NGF is not the primary component of ODF. Together, the results of this study indicated that the properties of the ODF are not mimicked by the neurotrophins or CNTF.