The relationship between myocardial lactate production and the severity and duration of ischemia was studied in globally ischemic, isolated rat and rabbit hearts. In both species, the rate of lactate production was not constant, despite a constant degree of ischemia; the coronary venous lactate concentration reached a peak value 10-15 minutes after the onset of ischemia and then decreased by 40-50% during 15-60m minutes of subsequent ischemia. The rate of lactate production in moles/min (concentration x flow rate) was decreased during more severe degrees of ischemia, despite an increase in venous lactate concentration. Maximum lactate production occurred with mild-to-moderate ischemia; during severe ischemia, lactate production was reduced 88% in the rat and 71% in the rabbot myocardium. A model of regional ischemia was constructed using the rates of lactate production determined in the globally ischemic, isolated hearts. Even under ideal conductions of a 'steady-state' degree of ischemia and optimal placement of the coronary sinus sampling catheter, calculated changes in the coronary sinus lactate level did not show a constant or directionally similar relationship to modeled changes in the ischemic condition. Our results indicate that indices of lactate metabolism may not reliably measure sequential changes in the amount or degree of ischemia.