Background: WHO/UNAIDS recommended that cotrimoxazole should be prescribed in Africa in HIV-infected adults with CD4 cell counts < 500 X 10(6)/I, while closely monitoring bacterial diseases in as many settings as possible. Methods: Prospective cohort study, describing bacterial morbidity in adults receiving cotrimoxazole prophylaxis (960 mg daily) between April 1996 and June 2000 in Abidjan, Cote d'lvoire. Results: Four-hundred and forty-eight adults (median baseline CD4 cell count 251 X 10(6)/I) were followed for a median time of 26 months. The rates of overall bacterial diseases and of serious bacterial diseases with hospital admission were 36.8/ 100 person-years (PY) and 11.3/100 PY, respectively. Bacterial diseases were the first causes of hospital admissions, followed by non-specific enteritis (10.2/100 PY), acute unexplained fever (8.4/100 PY), and tuberculosis (3.6/100 PY). Among serious bacterial diseases, the most frequent were enteritis (3.0/100 PY), invasive urogenital infections (2.5/100 PY), pneumonia (2.3/100 PY), bacteraemia with no focus (2.0/100 PY), upper respiratory tract infections (1.6/100 PY) and cutaneous infections (0.6/100 PY). Compared with patients with baseline CD4+ cell counts greater than or equal to 200 X 10(6)/I, other patients had an adjusted hazard ratio of serious bacterial diseases of 3.05 (95% confidence interval, 2.00-4.67; P < 0.001). Seventy-five bacterial strains were isolated during serious episodes including 29 non-typhi Salmonella,, 14 Escherichia coli, 12 Shigella spp, and 12 Streptococcus pneumoniae. \Discussion: Though with a medium-term rate half that of the short-term rate estimated under placebo before 1998 (26.1/100 PY), serious bacterial morbidity remains the first cause of hospital admission in adults receiving cotrimoxazole in this setting. (C) 2003 Lippincott Williams Wilkins.