The objective of this study was to test the hypothesis that the integrity of the large bowel wall in AIDS patients is compromised in a manner that favours the chronic translocation of bacteria and/or products of bacterial metabolism into the bloodstream. When such translocation occurs, it induces a characteristic stress/inflammatory response in the body. Urinary butyrate, a unique product of colonic microbial metabolism, was used to assess gut wall permeability. Excretion of the pro-inflammatory cytokine IL-6 in the urine was used as a marker for the stress/inflammatory response. Four groups of subjects were studied, controls (n = 12), HIV + (n = 35) and AIDS patients with (n = 14) and without (n = 17) weight loss. Results: measurable amounts of interleukin 6 (IL-6) and butyrate were found in the urine of all subjects. There were no significant differences in IL-6 excretion between the controls (0.68 +/- 0.64 pg/ml), asymptomatic HIV + subjects (0.59 +/- 0.37 pg/ml) and AIDS patients without weight loss (1.18 +/- 0.33 pg/ml) but IL-6 levels were significantly higher in the AIDS group with weight loss (4.02 +/- 1.26 pg/ml, P < 0.05). A similar pattern of results was found with interleukin 1 receptor antagonist (IL-1ra). Like IL-6 and (IL-1ra), urinary butyrate levels were increased in the AIDS patients with weight loss (2.83 +/- 0.67 mumol/l) relative to the controls (1.31 +/- 0.13 mumol/l, P < 0.05), with the HIV + patients (1.65 +/- 0.18 mumol/l) and AIDS patients without weight loss (1.90 +/- 0.22 mumol/l) falling in between. The data are consistent with a low, but chronic rate of bacteria and/or bacterial products seeping across a compromised colonic wall causing a chronic low stress response in AIDS patients.