Six volunteers with normal baseline intestinal biopsies orally ingested stool filtrate containing Hawaii agent. Two volunteers developed clinical gastroenteritis and an intestinal mucosal lesion with altered mucosal architecture, mucosal inflammation, and abnormal-appearing absorptive cells. This lesion was indistinguishable from the intestinal lesion demonstrated previously in volunteers who had ingested Norwalk agent. In addition, two of four asymptomatic volunteers developed the typical mucosal lesion. The third asymptomatic volunteer developed late, mild, nonspecific histologic changes. Biopsies from the fourth asymptomatic volunteer remained normal. These findings indicate that Hawaii agent, although apparently immunologically distinct from Norwalk agent, produces an identical lesion of the proximal small intestine. This suggests that this lesion is characteristic of viral gastroenteritis and not restricted to disease produced by one specific infectious inoculum.