Diarrhea occurs commonly in African human immunodeficiency virus (HIV) infections. A case-control (HIV-positive vs, -negative) study of adults with diarrhea was done in Lusaka, Zambia, to determine the prevalence of intestinal infection by HEp-2 cell-adherent Escherichia coli, Adherent E, coli were more common in HIV-positive patients with acute diarrhea than among HIV-negative controls (60% vs, 33%) and were found significantly more often in HIV-positive patients with chronic diarrhea than among HIV-negative controls with chronic diarrhea (79% vs, 17%, P < .002), Adherent strains were found significantly more often among HIV-positive patients (69%) than in 22 asymptomatic subjects (36%, P < .02). The HEp-2 cell adherence of the E, coli strains did not show a common pattern, Adherent bacteria were also observed in colonic biopsies from 32% of Zambians with chronic diarrhea who underwent endoscopy, Adherent E, coli may be an important cause of HIV-associated diarrhea in Zambia.