The isolated hearts of adult and neonatal guinea-pigs have been compared for changes in intracellular amino acids during calcium depletion and the loss of cellular proteins on calcium repletion. Taurine, in freshly excised ventricles of neonatal guinea-pig heart, at 10.5 +/- 0.5 mmol (kg wet weight)-1 (n = 5) is less than in the adult heart (13.0 +/- 0.6 mmol (kg wet weight)-1 (n = 5)) but still is the most abundant amino acid free in the sarcoplasm. A marked loss of tissue taurine in both neonatal and adult hearts (a fall to 3.5 +/- 0.25 mmol (kg wet weight)-1 in neonatal and 4.9 +/- 0.6 mmol (kg wet weight)-1 in adult hearts after 10 min) was induced by perfusion with Ca, Mg-free Tyrode solution. A fall in several of the alpha-amino acids was also seen during this manoeuvre. On reperfusion with normal Tyrode solution, a marked release of proteins (lactate dehydrogenase, creatine kinase and myoglobin) was observed, which showed a similar time course in both types of heart. Elevation of [Mg]o during calcium depletion reduced protein loss on calcium repletion in both neonatal and adult guinea-pig hearts. This effect was consistent with an effect of Mg2+ on the rise of [Na]i. A second effect of [Mg]o was to shift the time to peak protein loss, an effect greater in neonatal hearts and more pronounced for the proteins with larger molecular weight (lactate dehydrogenase > creatine kinase > myoglobin). This latter effect of Mg2+ would seem not to be due to an effect on capillary permeability because the presence of bovine serum albumin in the perfusate failed to produce a similar effect. Neonatal and adult guinea-pig hearts show a similar sensitivity to the calcium paradox and similar changes in tissue taurine during calcium depletion, and therefore contrast with rat and rabbit heart.