The neurotrophic effects of ebiratide, an ACTH4-9 analog, have been examined using both fetal rat septal cultures and aged rats. The 5-day treatment with ebiratide (10-100 pmol/ml) partially prevented neuronal degeneration that occurred in the cultures in which cells were sparsely plated. Ebiratide (10 pmol/ ml) increased choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities up to 1.5 and 1.2 times the respective control values in the sub-confluent cultures. AChE cytochemistry of the cultures has shown that ebiratide increased the stained area per cell. Ebiratide subcutaneously administered by constant infusion (10 nmol/body/hr) for 4 weeks elevated ChAT activities in the septum (35% over control), neocortex (79%) and hippocampus (89%) of aged rats. Thus, the present study indicates that ebiratide shares neurotrophic properties which may prove beneficial in the therapy for CNS degenerative disorders, especially Alzheimer's disease.