To determine the relationship of lung 201Tl activity during adenosine scintigraphy to the presence and extent of coronary artery disease, we investigated 132 subjects comprising 4 groups: 36 normal volunteers, 19 patients with angiographically normal coronaries, 29 patients with single-vessel (greater than 50% luminal stenosis) and 48 patients with multivessel coronary artery disease. Lung activity was quantified relative to maximal myocardial activity in both an early anterior planar image (pretomography) and the unprocessed tomographic image in the anterior projection. A good correlation was found for the lung-to-heart ratio assessed by planar and tomographic imaging (r = 0.83, p less than 0.0001), but the ratio was higher with planar imaging. The lung-to-heart ratio in the planar images was significantly higher in patients with multivessel disease compared to those with single-vessel disease (p less than 0.05) or volunteers and subjects with normal coronary arteries combined (p less than 0.001). A lung-to-heart ratio of greater than 0.45 in the planar images (upper 95% confidence limit for the normal subjects) was found in 6 (21%) single-vessel disease and 17 (35%) multivessel disease patients. Patients with elevated lung thallium activity during adenosine infusion had more hypoperfused myocardial segments (p = 0.007), more segments with redistribution (p = 0.04) and larger initial perfusion defect size (p = 0.04) than those with normal lung activity. Thus, evaluation of lung activity during adenosine thallium scintigraphy provides supplementary information regarding the severity of coronary artery disease and extent of myocardial hypoperfusion.