The objectives of this study were to evaluate characteristics associated with diarrhea, the effect of trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis on diarrhea, the response to treatment with ciprofloxacin and tinidazole (Cipro-TZ), and presence of enteric pathogens. Adults infected with human immunodeficiency virus with and without diarrhea served as cases and controls, respectively. Participants provided a medical history and underwent a physical examination. Blood was collected for CD4 cell counts and stool for culture. Cases were treated with Cipro-TZ. Factors associated with a risk of diarrhea included crowded living and no toilet (all P < 0.05). Protective variables (P < 0.05) included a CD4 count greater than 200 cells/mm(3) and TMP/SMX prophylaxis. Cases were more likely to have a pathogen identified (P = 0.05). Eighty-six percent of the cases responded to treatment. Important risk factors for diarrhea were identified. Protection by TMP/SMX reinforces the importance of prophylaxis. These data suggest that treatment with an antibiotic and anti-parasitic medication may be effective.