To determine the incidence, cause, and patterns of diarrhea during the first 2 years of life among infants infected perinatally with the human immunodeficiency virus (HIV). A cohort study in which infants were enrolled shortly after birth and followed up longitudinally using biweekly surveillance for the occurrence of diarrhea. Stool specimens collected at the onset of diarrhea were evaluated for enteropathogens. Infants who were infected with HIV were compared with uninfected infants. Infants born to HIV-infected women at the University of Maryland Hospital, Baltimore, were recruited at 0 to 3 months of age. This analysis included 58 infants enrolled in the cohort and followed up at least 15 months (unless death intervened) whose HIV status was established (18 HIV-infected infants and 40 HIV-uninfected infants). The overall incidence of diarrhea in HIV-infected infants was 3.2 episodes per 12 child-months compared with 1.5 episodes per 12 child-months among HIV-uninfected infants (incidence density ratio, 2.2; P < .05). An enteropathogen was identified in stool specimens collected during 20% of diarrheal episodes occurring in HIV-infected infants and during 25% of diarrheal episodes occurring in HIV-uninfected infants. Episodes that persisted for 14 days or longer were significantly more common among HIV-infected infants. The peak incidence of diarrhea occurred at 0 to 5 months of age for HIV-infected infants compared with 6 to 11 months for HIV-uninfected infants. Early onset of diarrhea (< 6 months old) in HIV-infected infants was associated with the later development of persistent episodes of diarrhea, and those with persistent episodes had more severe HIV infection, characterized by a significantly higher frequency of opportunistic infections and lower CD4+ T-lymphocyte counts by 1 year of age. Both acute and persistent episodes of diarrhea are major sources of morbidity in HIV-infected infants. Moreover, persistent diarrhea is a marker for rapid progression of HIV disease.