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 A₁ agonists 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 A₁ receptor sensitivity to adenosine without altering the sensitivity of the A₁ receptor 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.