To predict the nature of non-calcifying lung tumors, we performed a prospective study of 46 cases with L-[methyl 11C]methionine (MET, 24 cases) and 18F-fluorodeoxyglucose (FDG, 22 cases) using positron emission tomography (PET). Mean tumor/muscle radioactivity ratios are 5.3 +/- 2.0 (n = 14) for malignant and 1.9 +/- 0.9 (n = 10) for benign with MET (p less than 0.001), and 4.4 +/- 2.2 (n = 12) and 1.5 +/- 0.3 (n = 10), respectively, with FDG (p less than 0.001). The ratios indicate that malignant tumors have higher metabolic demand than benign lesions. Tumors less than 1 cm in diameter were difficult to accurately evaluate due to PET resolution. Compared to the diagnosis at pathology, the MET study showed a sensitivity of 93% (13/14), a specificity of 60% (6/10), and an accuracy of 79% (19/24). The FDG study showed 83% (10/12), 90% (9/10), 86% (19/22), respectively. No significant differences were observed between the two tracers. This study suggests that PET studies using either MET or FDG may be very useful for the differential diagnosis of lung tumors.