The effect of fish oil, melatonin or their combination, and dietary advice on cachexia and biochemistry variables reflecting cachexia were investigated in patients with advanced gastrointestinal cancer. Twenty-four patients not amenable to standard anticancer treatment and with documented weight loss and/or decreased serum albumin were included. They were randomised to 30 ml/day of fish oil, which provided 4.9 g of eicosapentaenoic acid and 3.2 g of docosahexanoic acid, or 18 mg/day of melatonin for 4 weeks. During the next 4 weeks, all patients had fish oil and melatonin. Serum or plasma was analysed for tumour necrosis factor-alpha, interleukin-1beta, soluble interleukin-2 receptor, interleukin-6 and interleukin-8, and the fatty acids eicosapentaenoic acid, docosahexanoic acid, arachidonic acid and linoleic acid. Serum levels of eicosapentaenoic acid and docosahexanoic acid increased as expected with fish oil. No major changes in biochemical variables and cytokines were observed with any intervention. In the fish oil group, five of 13 patients (38%) showed weight stabilisation or gain compared with three of 11 patients (27%) in the melatonin group. After combining interventions, approximately 63% of patients showed such responses.