Wasting in African AIDS patients is severe, and its aetiology is probably multifactorial: persistent diarrhoea, poverty and tuberculosis may all contribute. We report a cross-sectional study of body composition measured anthropometrically in 75 adult patients with HIV-related persistent diarrhoea in Lusaka, and its relationship to gastrointestinal infection and systemic immune activation assessed using serum neopterin and soluble tumour necrosis factor receptor (sTNF-R55) concentrations. Patients as a group were generally severely wasted (mean body mass index (BMI) 15.8 kg/m2, range 11-22), but the severity of wasting was related neither to oesophageal candidiasis nor to intestinal infection. In men but not women, all measures of nutritional status were negatively related to serum sTNF-R55 concentration (fat-free mass in men, r = -0.64; 95% CI: -0.80, -0.41; p < 0.0001). Some wasted patients had cutaneous features of malnutrition, again associated with higher sTNF55 concentrations, and two had peripheral oedema. The diarrhoea-wasting syndrome in this part of Africa seems to be associated with evidence of high cytokine activity in men, rather than oesophageal candidiasis or any particular intestinal opportunistic infection. This immune activation requires further investigation in the context of the sex difference we have observed.