1. The ubiquitous distribution of A1-adenosine receptors (A1AdoR) represents an impediment to achieve organ and/or response selectivity of A1AdoR agonists. Differential receptor reserve may be exploited to overcome this problem. We hypothesize that A1AdoR reserve is agonist-dependent and can be accurately estimated with Furchgott's method. 2. Concentration-response curves were constructed from measurement of the atrial monophasic action potential duration in guinea-pig, isolated hearts treated with R(-) N6-(2-phenylisopropyl)adenosine (R-PIA) or 2-chloro-N6-cyclopentyl-adenosine (CCPA) before and after treatment with the selective, irreversible A1AdoR antagonist 8-cyclopentyl-3-[3-[[4-(fluorosulphonyl)benzoyl]oxy]propyl]-1-prop ylxanthine (FSCPX). Using Furchgott's method, we determined the equilibrium dissociation constant (KA) of R-PIA and CCPA, and the fraction of non-inactivated A1AdoRs remaining after FSCPX treatment (q(functional)). Values of q(functional) were correlated to the fraction of specific binding sites after FSCPX treatment labelled by [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]-CPX) derived from saturation binding normalized to control (q(binding)). 3. Both R-PIA and CCPA are full A1AdoR agonists, but have significantly different potencies (pD2 [EC50]=6.84+/-0.04 [145 nM] vs 7.36+/-0.04 [44 nM], respectively), receptor affinities (pKA [KA]= 6.54+/-0.10 [288 nM] vs 6.13+/-0.03 [734 nM]), and pharmacological shift ratios defined as KA/EC50 (2.2+/-0.6 vs 15.9+/-1.5). Values for q(functional) and q(binding) were highly correlated (r2=0.96). The ratio between the intrinsic efficacies of CCPA and R-PIA derived from Furchgott's analysis was 5.9, a value similar to the ratio of 6.2-6.6 calculated from previously obtained binding data. 4. Radioligand binding studies validated the use of Furchgott's method to estimate A1AdoR reserve. A1AdoR reserve was agonist-dependent. CCPA was shown to be a high intrinsic efficacy, low affinity agonist, whereas R-PIA was found to be a low intrinsic efficacy, high affinity agonist.