Although weight loss is often a dominant symptom in patients with upper gastrointestinal malignancy, there is a lack of objective evidence describing changes in nutritional status and potential associations between weight loss, food intake, markers of systemic inflammation and stage of disease in such patients. Two hundred and twenty patients diagnosed with gastric/oesophageal cancer were studied. Patients underwent nutritional assessment consisting of calculation of body mass index, measurement of weight loss, dysphagia scoring and estimation of dietary intake. Serum acute-phase protein concentrations were determined by enzyme-linked immunosorbent assay. In all, 182 (83%) patients had lost weight at diagnosis (median loss, 7% body weight). Weight loss was associated with poor performance status, advanced disease stage, dysphagia, reduced dietary intake and elevated serum C-reactive protein (CRP) concentrations. Multiple regression identified dietary intake (estimate of effect, 38%), serum CRP concentrations (estimate of effect, 34%) and stage of disease (estimate of effect, 28%) as independent variables in determining degree of weight loss. Mechanisms other than reduced dietary intake or mechanical obstruction by the tumour appear to be involved in the nutritional decline in patients with gastro-oesophageal malignancy. Recognition that systemic inflammation plays a role in nutritional depletion may inform the development of appropriate therapeutic strategies to ameliorate weight loss, making patients more tolerant of cancer-modifying treatments such as chemotherapy.