The impact of age on functional sensitivity to A1-adenosine receptor activation was studied in Langendorff-perfused hearts from young (1–2 mo) and old (12–18 mo) male Wistar rats. Adenosine mediated bradycardia in young and old hearts, with sensitivity enhanced ∼10-fold in old [negative logarithm of EC50(pEC50) = 4.56 ± 0.11] versus young hearts (pEC50= 3.70 ± 0.09). Alternatively, the nonmetabolized A1agonists N6-cyclohexyladenosine and ( R)- N6-phenylisopropyladenosine were equipotent in young (pEC50= 7.43 ± 0.12 and 6.61 ± 0.19, respectively) and old hearts (pEC50= 7.07 ± 0.10 and 6.80 ± 0.11, respectively), suggesting a role for uptake and/or catabolism in age-related changes in adenosine sensitivity. In support of this suggestion, [3H]-adenosine uptake was approximately twofold greater in young than in old hearts (from 3–100 μM adenosine). However, although inhibition of adenosine deaminase and adenosine transport with 10 μM erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride and 10 μM S-(4-nitrobenzyl)-6-thioinosine increased adenosine sensitivity three- to fourfold, it failed to abolish the sensitivity difference in old (pEC50= 4.95 ± 0.08) versus young (pEC50= 4.29 ± 0.13) hearts. Data indicate that 1) age increases functional A1receptor sensitivity to adenosine without altering the sensitivity of the A1receptor itself, and 2) age impairs adenosine transport and/or catabolism, but this does not explain differing functional sensitivity to adenosine. This increased functional sensitivity to adenosine may have physiological significance in the older heart.