Understanding the extent to which changes in whole-body protein kinetics contribute to the commonly observed weight loss and decrease in lean body mass (LBM) in patients with cancer is currently obscured by conflicting reports in the literature. While several studies have reported significant increases in whole-body protein turnover (WBPT), synthesis (WBPS), and catabolism (WBPC) in patients with cancer, others have failed to confirm these observations. We have measured whole-body protein kinetics using a primed constant infusion of 15N-glycine in a homogenous group of 32 newly diagnosed advanced lung cancer patients with comparable staging and before any antineoplastic treatment, and in 19 normal healthy volunteer controls. Urinary urea and ammonia 15N enrichment was determined in individually collected urine samples obtained during the 24-hour study period and averaged for the determination of protein kinetics. During the last 6 hours of urine collection, samples were obtained hourly for determination of 15N plateau enrichment. Twenty-four-hour urinary nitrogen and creatinine excretion was determined from 24-hour pooled urine samples. Resting metabolic expenditure (RME) was determined by indirect calorimetry and LBM was estimated from deuterium oxide dilution. Age, body weight, LBM, RME, and 24-hour urinary nitrogen excretion did not differ between cancer and control subjects. WBPT, WBPC, and WBPS (g/kg/d) were significantly increased in lung cancer patients. However, when the same results were expressed either per kilogram LBM or per gram 24-hour urinary creatinine excretion, WBPT, WBPC, and WBPS rates were not statistically different from those of the controls. Net protein synthesis (WBPS - WBPT) was not different from that of the controls, regardless of how data were expressed. These results reveal that protein kinetics in the lung cancer patients were not significantly different from those of the control group when normalized to active muscle mass, and suggest that newly diagnosed noncachectic advanced lung cancer patients do not exhibit a significant increase in whole-body protein kinetic rates. © 1993.