Purpose: Skeletal muscle wasting and weight loss are characteristic features of cancer cachexia and contribute to impaired function, increased morbidity and poor tolerance of chemotherapy. This study used a novel technique to measure habitual myofibrillar protein synthesis in cancer patients compared with healthy controls. Experimental design: An oral heavy water (87.5g deuterium oxide) tracer was administered as a single dose. Serum samples were taken over the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment was measured in body water, serum alanine and alanine in the myofibrillar component of muscle using Gas Chromatography-Pyrolysis-Isotope Ratio Mass Spectrometry and the protein synthesis rate calculated from the rate of tracer incorporation. Net change in muscle mass over the preceding 3 months was calculated from serial CT scans and allowed estimation of protein breakdown. Results: 7 healthy volunteers, 6 weight-stable and 7 weight-losing (?5% weight loss) patients undergoing surgery for upper GI cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6100d. Myofibrillar protein fractional synthetic rate was 0.058, 0.061 and 0.073 h in controls, weight-stable and weight-losing patients respectively. Weight-losing patients had higher synthetic rates than controls (p=0.03). Conclusion: Contrary to previous studies, there was no evidence of suppression of myofibrillar protein synthesis in patients with cancer cachexia. Our finding implies a small increase in muscle breakdown may account for muscle wasting.