To determine whether liposomes (microscopic phospholipid vesicles) may be useful in delivering drugs to a region of myocardial ischemia, we studied the concentration of positively charged and neutral liposomes containing 131I-albumin and horseradish peroxidase in ischemic myocardium of 20 dogs during the first 4 hours of experimental myocardial infarction. We studied the interaction of liposomes containing fluorescent dyes and horseradish peroxidase with isolated contracting cardiac myocytes. We found that positively charged and neutral liposomes accumulated in poorly perfused myocardium and that positively charged liposomes accumulated in the ischemic region to a greater extent than neutral liposomes [138 +/- 21 vs. 81 +/- 9% (mean +/- SE) of the concentration of liposomes in uninvolved myocardium]. Electron microscopic examination of this myocardium showed liposome contents to be located in the vascular space, in endothelial cells, and in ischemic myocytes. We found high potassium environment and that liposomal contents were scattered throughout the interior of the cells in the electron micrographs of some of the isolated myocytes. Anoxia alone for 20-30 minutes did not modify the liposome-isolated myocyte interaction or cause depolarization of the cells. We conclude that liposomes may be useful as drug carriers to depolarized ischemic myocardium, although significant uptake by normal myocardial cells cannot be expected with lecithin, cholesterol, and octadecylamine liposomes we used.