The involvement of intestinal damage in experimental African trypanosomiasis was investigated in rats infected with Trypanosoma brucei brucei by measuring the urinary excretion of the previously administered non-metabolizable sugar probes, D-mannitol and lactulose, and the flux of FITC-dextran across isolated, everted gut segments. There was increased urinary recovery and flux of the sugar probes across the intestine which were significant (P<0·05) and maximum at day 21 of the infection, but subsequently reduced, in the terminal stages of infection (day 33 p.i.). In the case of the everted sac studies the reductions were to less than 25% control values (P<0·001). Levels of circulating endotoxin were increased approximately 3-fold at day 21 p.i., 4-fold at day 33 p.i., compared to controls. At day 21 there was a significant correlation (r = 0·63, P<0·01) between the log endotoxin levels and the increased sugar excretion expressed as the lactulose/mannitol ratios. Histological studies showed damage to the villi, wall thinning and marked cellular infiltrations, which were very prominent in the proximal jejunum and duodenum. These results demonstrate that during trypanosome infections in rats, increased intestinal leakage and increased circulating endotoxins are significant pathological features.