The effects of piretanide upon mechanical activity and pharmacological reactivity of vascular and myocardial tissues from normotensive rats were investigated. Magnitude of phasic contractions of isolated rat portal vein was diminished by the drug in a dose-related manner; contractile depression induced by piretanide (10−4 M) was less in the presence of insulin (0.1 U/mL), glucose (22 mM) or pyruvate (5 mM). Responses to KCl (90 mM), or norepinephrine (2.5 × 10−5 M) were also reduced. Contractile activity of atria and ventricle strips was diminished only when piretanide reached 10−4 M. Results support direct actions of piretanide upon cardiac and vascular tissues. Possible mechanisms of action are discussed.