Eight patients with ischemic heart disease performed isometric handgrip of five minutes' duration at 30% of their maximum voluntary contraction, before and after administration of 0.4 mg sublingual nitroglycerin (NTG). Although isometric exercise resulted in similar rise of left ventricular systolic pressure (LVSP) before and after NTG, the level of LVSP during the post NTG effort was lower. Heart rate, cardiac index, stroke index, left ventricular stroke work index, and systemic resistance were not different during the pre- and post NTG exercise. Left ventricular end-diastolic pressure rose to a significantly lower level (18.3 +/- 14.4 mm Hg) during the post NTG handgrip than during the pre NTG effort (31.4 +/- 17.6 mm Hg, P less than 0.005). It is concluded that NTG reduces preload and afterload both at rest and during isometric exercise and improves left ventricular performance during isometric exercise.