Abstract 1. 1. The low- and high- K M cyclic AMP phosphodiesterase (cAMP PDE) activity in cerebral cortex, striatum, hypothalamus and hippocampus of young (4–5-month-old) and aged (22-month-old) rats has been studied. 2. 2. A significant rise in the high- K M cAMP PDE activity in the cerebral cortex, hypothalamus and hippocampus in aged rats has been found. 3. 3. The activity of the low- K M cAMP PDE does not change during senescence in all the brain structures studied. 4. 4. In a series of increased concentrations (from 5 × 10 −4 to 1 × 10 −5 M) adafenoxate inhibits low- and high- K M cAMP PDE in most of the brain structures studied in both age groups. 5. 5. The present results provide evidence for realization of the CNS effects of adafenoxate through inhibition of cAMP PDE activity and regulation of the intracellular level of cAMP.