Aged rats were tested for place navigation in a circular water maze for spatial memory ability at 18 and 30 months of age; 45% of the 18-month- old rats displayed impaired place navigation performance relative to young control rats, while essentially all of the 30-month-old rats were impaired. The aged impaired rats were retested twice during NGF or vehicle infusion in the right lateral ventricle. In the 18-month-old group, NGF-infused rats showed improved retention of previously acquired place navigation performance and improved spatial acuity over the former platform site when the invisible platform was removed. NGF infusion also had a significant effect in the much more severely impaired 30-month-old rats: while the vehicle-infused aged rats showed a progressive decline in the performance between the first and second test weeks, the performance of the NGF-infused rats remained stable throughout the infusion period. The interpretation of these effects in the oldest animals, however, was confounded by a progressive decline in swim speed seen in the vehicle-infused animals. The 30-month-old vehicle-infused control rats showed a significant cell loss and cell shrinkage relative to the young control rats in the septal/diagonal band area, the striatum, and the nucleus basalis as assessed by NGF- receptor (NGFr) and ChAT double-label immunocytochemistry. A significant increase in the size but not in the number of cells was observed on the side of the NGF infusion in the 30-month-old NGF- infused rats.