Increased levels of circulating endotoxins are a feature of both human and experimental African trypanosomiasis. Studies with rats and mice have shown that these may originate from intestinal damage with altered permeability of the gut epithelium. Endotoxins are potent immunomodulatory substances which can initiate the production of a range of cytokines and mediators from different cell types. In rats infected with T.b. brucei we have examined possible associations of the endotoxin increases with increases in levels of TNF-α, IL-1β, IL-6, IFN-γ and nitric oxide (NO). Significant increases in each substance occurred at days 21 and 33 post-infection (p.i.). The increases in cytokines were highly correlated with the endotoxin levels (e.g. at day 21 p.i. the correlation–regression values were as follows: TNF-α, r = 0·9, P<0·01; IL-1β, r = 0·83, P<0·01; IL-6, r = 0·9, P<0·01; IFN-γ, r = 0·7, P<0·01). There were also strong correlations between the increased levels of several individual cytokines. Biopsies of chopped sections of small intestine tissues of rats showed a parallel production of cytokines, again with significant correlations with the circulating endotoxins. The production of NO and cytokines by the intestine may be associated with the increased transepithelial permeability which occurs during the infection.