Neurotrophins are a family of neurotrophic factors with considerable structural homology. We used sensitive and specific two-site enzyme immunoassays to assess age-associated changes in levels of three neurotrophins++-+-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3)--in the hippocampus of Fischer 344 rats. Expressions of these proteins and their mRNAs were compared in the same animals. More than 200 ng of BDNF per gram of tissue was detected in the hippocampus of 2-month-old rats. This amount was two and 100 times greater than that of NT-3 and NGF, respectively. The levels of BDNF and NT-3 increased further 2-6 months after birth, whereas NGF content declined during this period, and the altered protein levels of all three neurotrophins were maintained 6-18 months postnatally. In contrast to the patterns of protein expression, BDNF mRNA levels increased during both of these periods, and the NT-3 mRNA levels appeared to decline. Changes in the expression of BDNF mRNA and NGF protein were opposite to those reported to occur in Alzheimer's disease. These results suggest that, during normal aging in rats, neurotrophin expression is regulated independently at both the mRNA and posttranslational levels. Any deficiency in their regulation might contribute to neurodegenerative disorders.