The age-dependent effect of a calcium-free medium on myocardial mechanical function, high energy phosphates (HEP), as well as HEP and creatine phosphokinase (CPK) release was studied in the arterially perfused rabbit heart. The effect in the newborn was significantly less than in the adult with the transition occurring between two and five weeks of age. Thirty minutes of Ca2+ depletion had no significant effect on tissue high energy phosphate, creatine phosphokinase (CPK) release and creatine release. During Ca2+ repletion, the recovery in developed tension (DT) and +dT/dt (max) in the newborn was significantly greater than in the adult. The increase in resting tension in the newborn was significantly less in the newborn than in the adult. A significant decrease in tissue adenosine triphosphate (ATP) and CP was observed after Ca repletion following 5 minute Ca depletion in the adult and only after 30 minutes depletion in the newborn. Significant increases in CPK, creatine, and adenine nucleotide release were observed during Ca2+ repletion and the amounts released in the adult were significantly greater than in the newborn. There was a significant correlation between the percent recovery of +dT/dt (max) and tissue ATP content in both age groups. In addition, there was an inverse correlation between the recovery of +dT/dt (max) and log CPK release. These data indicate that the Ca2+ paradox effect is minimal in the newborn rabbit and becomes similar to that of the adult at five weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)