Cultured myocytes isolated from neonatal rats of 3-4 days old was employed as a model for the study of the mechanisms involved in the cardiotoxicity of adriamycin and daunomycin analoges. Creatine kinase and LDH leakage were used as the parameters for determining the extent of toxicity. There was a good correlation between various papameters employed for cell death. The toxicity studies using LDH leakage as a parameter and electron microscopy done in this laboratory earlier correlated with these results. Minor structural variations in the structure of adriamycin and daunomycin markedly changed the extent of toxicity. It appears from these studies that the initial event leading to cardiotoxicity is a marked reduction in the ATP and cretine phosphate.