Ultrastructural changes in the myocardium during intermittent warm blood cardioplegia were studied in 12 dogs. During cardiopulmonary bypass, dogs received three 5-minute periods of warm blood cardioplegia, interrupted by three 10-minute episodes of ischemia in group A or three 20-minute episodes of ischemia in group B. Biopsy specimens were taken from the right ventricle before each cardioplegic infusion and at the end of the aortic cross-clamp period to analyze ultrastructural changes. Functional recovery was measured after cardiopulmonary bypass. Mild and principally reversible ultrastructural changes were observed in group A. In group B, moderate ultrastructural changes were observed, and these changes suggested cumulative ischemic injury. Functional recovery was good in group A, but significantly deteriorated in group B. We concluded that three 10-minute interruptions of warm blood cardioplegia cause mild ultrastructural changes and seem to be safe, but three 20-minute interruptions cause cumulative ischemic injury in normal dog hearts.