Solutions of KCl (1%, 10% and 31.2%) administered into the pericardial fluid or applied onto the surface of the heart evoked a dome-like change of the ECG in dogs, rats and guinea-pigs and led to myocardial infarction in 3-5 days. Both the acute changes in ECG and the infarction itself could be prevented by the application of pericardial fluid samples and by administration of three synthetic compounds onto the heart surface. The same substances also inhibited the development of ECG changes elicited by general hypoxia due to stopping artificial respiration. The existence of a peculiar myocardial space beginning with outer pores and reaching the myocardial cells through connective tissue pathways is postulated. Earlier studies showed that 125I-labelled albumin applied to the epicardial surface through a filter paper reached the endomyocardium through some intramyocardial pathways beginning with epicardial pores. In the present experiments intrapericardial application of India ink led to obstruction of these pores and thus prevented the infarction elicited by intrapericardial administration of KCl solutions. This space, being distinct from that accessible from the coronary arteries, serves for transfer of various substances into the myocardium, while other compounds (e.g. noradrenaline) are not effective through this pathway. Oxygen reaching this space from the epicardial surface protects the myocardium from the damaging effects of hypoxia and KCl.