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The clinical course of HIV infection is frequently different among infants and children from that in adults. In adults among the most common sources of morbidity related to therapy are adverse drug reactions, notably to trimethoprim-sulfamethoxazole. Although there are case reports of serious adverse reactions to trimethoprim-sulfamethoxazole among infants and children with HIV infection, the precise rate and clinical characteristics of these adverse reactions among HIV-infected children are unknown.We reviewed the clinical records of all children referred to a regional HIV clinic in a 6-year period. Therapy and suspected adverse drug reactions to therapy were reviewed by one of the investigators not involved in patient care. Adverse drug reactions were identified and characterized according to previously established criteria.During this time 78 children were referred for assessment of possible HIV infection, 45 of whom were ultimately determined to have the infection. Twenty-five were treated with trimethoprim-sulfamethoxazole, 15 (60%) of whom tolerated therapy and 10 (40%) of whom had adverse reactions. The most common type of adverse reaction was erythema multiforme (70%), followed by neutropenia (20%) and Stevens-Johnson syndrome (10%). In two patients a serious adverse reaction to trimethoprim-sulfamethoxazole led to the diagnosis of HIV infection.The overall incidence and type of serious adverse reactions to trimethoprim-sulfamethoxazole among infants and children with HIV infection appear to be similar to those among adults.