Campylobacter hyointestinalis was isolated from stool specimens of four persons, all of whom were experiencing nonbloody, watery diarrhea. The youngest (8 months of age) and the oldest (79 years of age) individuals were females, and the other two were homosexual men. C. hyointestinalis was the only clinically significant pathogen isolated from stool specimens for three of the individuals. In case 3 (involving a 37-year-old homosexual man), Entamoeba histolytica and Shigella sonnei were also present in the stool. The identification of all C. hyointestinalis strains was made biochemically and confirmed by DNA hybridization. This study documented the isolation of C. hyointestinalis from four patients with diarrhea, and our findings suggest that the clinical significance of Campylobacter species must be expanded to include C. hyointestinalis as a potential cause of human gastrointestinal disease.