To determine the influence of smoking on lung uptake of technetium-99m tetrofosmin (Tc-TF) during myocardial perfusion imaging, we examined 50 healthy subjects with normal myocardial perfusion single photon emission computed tomography findings, normal coronary angiograms, and no evidence of left ventricular hypertrophy. The 50 healthy subjects were divided into two groups. Group 1: 25 healthy subjects had smoking histories of at least 10 pack-years. Group 2: 25 healthy subjects were nonsmokers. Lung to heart ratios (L/H ratios) calculated from anterior planar images during exercise and rest states of Tc-TF myocardial perfusion imaging were obtained for all of the 50 healthy subjects. L/H ratios calculated from Tc-TF myocardial perfusion imaging in smokers were significantly higher than in nonsmokers during both exercise and rest states. However, no significant difference in L/H ratios was found between exercise and rest states in smokers and nonsmokers. In addition, a positive but nonsignificant correlation was found between smoking pack-years and either rest or exercise L/H ratios. When L/H ratios are used as a clinical diagnostic tool in Tc-TF myocardial perfusion imaging, we must consider that L/H ratios in smokers are higher than in nonsmokers.