AGE-related changes of A(1) and A(2a) adenosine receptor binding characteristics were investigated in three regions of the rat brain using the A(1) selective antagonist [H-3]DPCPX, and the A(2a) selective agonist [H-3]CGS 21680. The density of A(1) binding sites in aged rats (24 months) was decreased by 33% in the hippocampus and by 60% in the cortex and was unchanged in the striatum when compared with young adult rats (6 weeks), with no change in K-D. There were also age-related changes in the density of A(2a) binding sites: in the cortex, there was a 94% increase in the number of [H-3]CGS 21680 binding sites in aged rats compared with young rats, and a similar tendency was observed in the hippocampus (32% increase in A(2a) binding sites in aged rats), with no change in K-D; in the striatum there was a tendency for a decrease (22%) in the number of [H-3]CGS 21680 binding sites in aged rats, and a decrease in K-D. These results suggest that there are age-related changes in the balance between inhibitory A(1)- and excitatory A(2a)-adenosine receptor-mediated actions, which vary in different brain areas: in the cortex and hippocampus, the balance might be shifted towards adenosine-mediated excitatory actions, since there is an increase in the number of A(2a) receptors and a decrease in the number of A(1) receptors upon ageing. In contrast, in the striatum, the A(1)/A(2a) ratio might be only slightly affected upon ageing.