During the -adrenergic receptor (-AR) mediated stress-response in the heart, the relations between functional responses and metabolism are ill-defined, with the distinction between ₁- and ₂-AR subtypes creating further complexity. Specific outstanding questions include the temporal relation between inotropic and chronotropic responses and their metabolic correlates. We sought to elucidate the relative magnitudes and temporal dynamics of the response to ₁- and ₂-AR stimulation, and the energy expenditure and bioenergetic state related to these responses in the isolated perfused rat heart. Inotropic (left-ventricular developed pressure, LVDP, and dP/dt), chronotropic (heart rate, HR), and metabolic responses were measured during ₁- (n=9; agonist: norepinephrine) and ₂-AR (n=9: agonist: zinterol) stimulation. Oxygen consumption (MVO₂) was measured using fiber-optic oximetry, and high-energy phosphate levels and intracellular pH were measured using ³¹P NMR spectroscopy. A multiple-dose protocol was used, with near-maximal -AR stimulation at the highest doses. In both ₁ and ₂ groups, there were dose-dependent increases in LVDP, dP/dt, heart rate (HR) and MVO₂. The inotropic response showed more rapid onset, washout and variation during dose than did the chronotropic response, and was closely correlated with MVO₂. This suggests that myocardial bioenergetic state is more closely related to inotropic response than to chronotropic response. In addition, stimulation of the ₁-AR resulted in a greater magnitude and rate of onset of inotropic and MVO₂ responses than did ₂-AR stimulation during maximal stimulation. However, a similar decrease in intracellular energy charge was seen in the two groups, consistent with a greater rate of oxidative phosphorylation during ₁- than during ₂-AR stimulation.