Opiates, like morphine, were long known to produce changes in blood pressure and cardiac functions. However, the nature of these changes are a subject of continuous controversy. The substantial differences in the opiate effects on the cardiovascular system is also apparent in more recent studies using enkephalins, beta-endorphin and dynorphins. The present review is aimed to indicate the source of the variations in the experimental data and analyze the relative contribution of different experimental factors to the observed effects of opiates and opioid peptides on the cardiovascular system. The major factors which contribute to the nature of the opioid effect on the cardiovascular system are: anesthesia, species, dose, site of action in the brain, respiratory changes and receptor specificity. However, the cardiovascular status per se is an important determinant of the opiates and opioid peptide effects on hemodynamic functions as indicated in states of hypertension and shock. A newly described factor is the plasticity of the opioid receptor system which changes its level and distribution pattern in different physiological and pathophysiological states. This review emphasizes the importance of utilization of highly specific ligands to opiate receptors administered to discrete brain areas in the conscious animal.