The aim of this study was to assess the influence of incremental nitroglycerin infusion (NTG+Inf) on the myocardial uptake of Tc-99m-tetrofosmin (TF) in order to determine whether nitrates enhance the detection of viable myocardium with TF in patients with coronary artery disease (CAD) and left ventricular dysfunction. Fifty patients (39 males, 11 females; 54+/-11 years) with previous myocardial infarction and left ventricular dysfunction, who had been referred for coronary revascularization procedures, were studied. Myocardial single-photon emission tomography (SPET) images were obtained I h after injection of 750 MBq TF at baseline and after NTG+Inf, using a 2 day protocol. NTG+Inf was performed starting at 0.4 mug.kg(-1).min(-1), with equal increments every 5 min up to 2 mug.kg(-1)-min(-1). Within 1 week of the TF study, rest-redistribution (R-RD) Tl-201 SPET was performed after the injection of 111 MBq Tl-201. For each study, quantitative analysis was performed in 17 segments. Viability was defined as the presence of tracer uptake of >50% of the peak activity on baseline studies or reversibility. There was significant correlation between quantitative regional RD Tl-201 activity and TF activity after NTG+Inf (r = 0.90, P < 0.001). Of the 131 segments with severely reduced tracer uptake on resting TF images, 34 (26%) were reversible, showing increased tracer uptake after NTG+Inf (from 41%+/-7% to 57%+/-12% of peak activity; P < 0.001). All reversible segments after NTG+Inf had viability criteria on Tl-201 studies. There was 95% concordance between TF with NTG+Inf and RD Tl-201 imaging with regard to the presence of myocardial viability. We conclude that TF imaging with incremental NTG+Inf improves the detection of ischaemic but viable myocardium, correlating with the viability criteria observed on Tl-201 studies. When the advantages of TF imaging are considered, rest TF imaging with NTG+Inf may be a practical diagnostic protocol in patients with CAD and left ventricular dysfunction who are being considered for revascularization. ((C) 2003 Lippincott Williams Wilkins).