Adherence to antiretroviral (ART) therapy, as reported by children caregivers, was investigated and compared with physicians' estimates of adherence. Two parallel structured questionnaires were administered to caregivers of 129 HIV-infected children and to their physicians in seven different Italian reference centers. Doses omitted in the last four days were recorded. Perfect adherence (>95% of prescribed doses taken in the last four days before interview) was reported by caregivers of 103 (79%) children. Five children (5%) omitted one dose of any ART drug in four days and were considered adherent. Low (<95 but >80% of doses) and poor (<80% of doses) adherence were reported by 15 (12%) and six (5%) caregivers, respectively. Forty-eight children (37%) were judged to be non-adherent by their physicians, including 35 children who were receiving all the prescribed doses according to caregivers. The physicians identified eight out of the 21 non-adherent children as adherent. Non-adherence estimates by physicians closely correlated with poor clinical conditions. These data indicate that adherence is a major problem but there is a clear discrepancy between caregiver reports and physician judgement. The results underline the need of close surveillance of adherence in HIV-positive children in order to evaluate the effectiveness of ART therapy.