Giardia lamblia is known to produce functional and structural derangement of the small intestine but the pathogenesis of this defect is not clear. To examine this, mucosal scrapings from the small intestine of mice were incubated with human G. lamblia trophozoites. The integrity of the mucosal cells was assessed by their ability to exclude trypan blue, and by the levels of brush border lactase, sucrase and maltase. As judged by the trypan blue test, more mucosal cells incubated with G. lamblia were found to be damaged than were in the control groups I (mucosal cells alone) and III (mucosal cells plus Giardia culture media). Similar results were obtained with disaccharidases where again the mucosal cells incubated with G. lamblia showed a statistically significant reduction in the activity of lactase, sucrase and maltase compared to that in the control groups. These findings suggest that G. lamblia causes direct damage to the small intestinal epithelial cells and that this effect is not mediated through factors such as bacterial proliferation, bile salt deconjugation and immunological reactions.