Myocardial O2 delivery and changes in myocardial lactate metabolism during marked hypoxaemia (PaO2 5-5.4 kPa, Sa O2 70-75%) produced by 12% O2 breathing were studied in 12 healthy subjects at rest and during supine exercise up to maximal intensity. Blood for O2 and lactate analyses was sampled from catheters in an artery (a) and the coronary sinus (cs) and coronary sinus blood flow (CSBF) was measured by thermodilution. Lactate metabolism was evaluated in a subgroup of the subjects using i.v. infusion of [14C]lactate. At rest and during submaximal exercise up to heart rate 156 beats min-1 myocardial O2 uptake (MQO2) was maintained at the same level during hypoxaemia as during normoxaemia. This was achieved at rest mainly by a more complete O2 extraction, during exercise entirely by greater CSBF. During maximal exercise CSBF was 35% greater during hypoxaemia than normoxaemia, while there was no difference in cs O2 saturation. Maximal MQO2 was smaller during hypoxaemia than normoxaemia in spite of no difference in rate pressure product. The a-cs difference of lactate was reduced during hypoxaemia and there was a significant myocardial release of lactate, as calculated from [14C]lactate data, during hypoxaemic exercise, but not during hypoxaemic rest or normoxaemic rest and exercise. It is concluded that the heart has a coronary flow reserve of about 35%, which can be utilised under hypoxaemia. When this reserve is insufficient to supply the myocardium with oxygen lactate is produced to cover part of the myocardial ATP regeneration.