Objective:To determine whether a mucosal cytokine‐mediated inflammatory response is involved in cryptosporidial or microsporidial diarrhoea, as well as in diarrhoea of unknown origin in HIV‐infected patients.Design:Prospective study.Methods:Jejunal biopsies were obtained from HIV‐infected patients with diarrhoea. Controls were HIV‐infected and HIV‐seronegative patients without diarrhoea. Two biopsies were homogenized immediately and two other biopsies were first cultured for 20 h. Cytokines [tumour necrosis factor (TNF), interleukin (IL)‐1&bgr;, IL‐6, IL‐8, IL‐10], soluble TNF receptors (sTNFR) p55 and p75, and soluble IL‐2 receptor (sIL‐2R) were assessed in the homogenates and in the supernatants by sandwich enzyme‐linked immunosorbent or enzyme‐linked binding assays. The cytokine receptors were also measured in serum.Results:Six HIV‐infected patients with cryptosporidiosis, six with microsporidiosis, seven with diarrhoea of unknown origin, seven without diarrhoea, and seven HIV‐seronegative patients were eligible. Four patients were excluded because of the presence of other pathogens. No cytokines were detected in immediately homogenized jejunal tissue. Following culture, IL‐6 and IL‐8 levels were higher in HIV‐infected patients with diarrhoea of unknown origin than in HIV‐seronegative controls without diarrhoea, although this was not statistically significant. No differences in serum or post‐culture supernatant sTNFR p55 and p75 levels existed between the HIV‐infected patients with or without diarrhoea. sTNFR, IL‐1&bgr;, IL‐10 and the sIL‐2R were only detected in low amounts or not at all, and were equally distributed among all patient groups.Conclusions:This study indicates that mucosal cytokine‐mediated inflammatory responses do not play an important role in the pathogenesis of different types of diarrhoea in HIV‐infected patients. These results do not support the use of immunomodulatory therapy in these patients.AIDS 1995,9:367‐373