High affinity uptake of cAMP by slices of rat cerebral cortex was found to be inhibited by specific coronary vasodilators dilazep and hexobendine, but it was insensitive to a wide variety of centrally-acting drugs. Experiments using subcellular fractionation of cortical homogenates indicated preferential association of cAMP uptake with fractions rich in synaptosomes. Furthermore, autoradiographical studies showed that cAMP uptake by cerebellar slices was particularly strong in the molecular layer which is known to have a relatively high density of synaptic terminals. The present results suggest that high affinity uptake of cAMP is located in the vicinity of synaptic contacts, probably in nerve terminals. The data on the effects of drugs, especially the inhibition by hexobendine and dilazep, offer a pharmacological means to investigate a possible role of cAMP uptake in synaptic transmission.