The aim of this study was to determine whether intestinal xenografts could recapitulate human in utero development by using disaccharidases as markers. Twenty-week-old fetal intestine was transplanted into immunocompromised mice and was followed. At 20-wk of gestation, the fetal human intestine was morphologically developed with high sucrase and trehalase but had low lactase activities. By 9-wk posttransplantation, jejunal xenografts were morphologically and functionally developed and were then monitored for </=6 mo. Both sucrase and trehalase activities remained unchanged, but lactase activity increased in a manner similar to that described in in utero development. Changes in sucrase and lactase activities were paralleled by protein levels. Cortisone acetate treatment at 20-wk posttransplantation accelerated the ontogeny of lactase but did not alter sucrase and trehalase activities. Biopsies from 1- and 2-yr-old infant intestine showed that all activities, except trehalase in the proximal intestine, corresponded to the levels found in jejunal xenografts at 24 wk posttransplantation. These studies suggest that 20-wk-old fetal intestine has the extrauterine developmental potential to follow normal intrauterine ontogeny as a xenograft.