Undifferentiated PC12 cells contain detectable levels of the nervous-specific protein B-50/GAP-43. Upon treatment with NGF or change of culture medium, B-50/GAP-43 levels remained unchanged during the first 12 hours while neuritogenesis starts. Both, B-50/GAP-43 levels and neurite outgrowth peak at 24 hours. These results suggest that in PC12 cells the amount of B-50 already present is sufficient to support the start of NGF-induced neuritogenesis, presumably by translocation from cytosolic compartments to the membrane. Addition of DEX reversed the rise in B-50/GAP-43 levels induced by either the change of medium or by NGF. In contrast, neurite outgrowth was inhibited to a lesser extent, although after 36 hours of pretreatment with DEX neurite length was lower than control. NGF was capable of enhancing B-50/GAP-43 levels both in the presence and absence of DEX. This corroborates data from others, who concluded that DEX and NGF exert their effects through different mechanisms, e.g., transcription versus mRNA stabilization, respectively. The inhibitory effect of DEX under various conditions on both B-50 expression and neurite outgrowth in the normal PC12 cell line demonstrates the tight coupling of these parameters that might be indicative of a threshold effect of B-50 levels on neurite outgrowth.