A difficult problem in coronary arteriography is the assessment of the hemodynamic significance of stenoses that appear angiographically to be of only moderate severity (25 to 75% diameter narrowing). This is particularly important in patients who may be candidates for invasive therapy, such as percutaneous transluminal coronary angioplasty (PTCA) or coronary bypass surgery. To determine the significance of such lesions, we measured transstenotic coronary pressure gradients in 15 patients with angiographically moderate stenoses. For comparison, similar measurements were made in 17 patients with severe stenoses (more than 75% diameter narrowing) being considered for PTCA. The transstenotic pressure gradients were measured with a 2.0Fr polyvinyl chloride catheter cleared of microbubbles of air by flushing with carbon dioxide and degassed saline solution and attached to a low-volume displacement transducer for optimal frequency response. Mean transstenotic pressure gradients greater than 10 mm Hg at rest or more than 20 mm Hg under conditions of high coronary blood flow, as induced by Renografin 76, appeared to be associated with objective evidence of myocardial ischemia and symptomatic relief from PTCA. Smaller pressure gradients occurred in patients whose symptoms probably were not ischemic in nature. Transstenotic pressure gradient determination performed at the time of diagnostic catheterization may provide assistance in clinical decision-making in selected patients with angiographically moderate stenoses.