This review analyses the present knowledge on differences in human and animal heart preparations in respect to positive inotropic stimulation. The pharmacological effects of new positive inotropic drugs usually are evaluated in cardiac preparations from healthy and young animals. Human myocardium, especially from patients with heart failure has, however, distinctly different properties in respect to the positive inotropic effectiveness of several agents. This fact prohibits the extrapolation of results of experiments in laboratory animals to the diseased human heart. The partial ineffectiveness of several established positive inotropic substances in papillary muscles from failing human hearts indicates a membrane defect not present in healthy animal myocardium.