Thyroid hormone has profound effects on the heart and cardiovascular system. Systemic vascular resistance is uniformly decreased in both naturally occurring and experimental hyperthyroidism, and it is increased in thyroid hormone deficiency. Because vascular smooth muscle cell contraction is a major determinant of systemic vascular resistance, the present studies were designed to address the acute effects of the thyroid hormones, specifically triiodothyronine, on vascular smooth muscle cell contractile activity. Our data indicate that triiodothyronine causes smooth muscle relaxation; this property may account for some of its marked effects on the cardiovascular system. As a novel vasodilatory agent, the potential therapeutic implications for triiodothyronine may be numerous.