Objectives. To compare disease severity as judged by duration of ventilation, inotrope use and mortality in children ventilated for respiratory syncytial virus (RSV)-positive lower respiratory tract infection (LRTI) with and without elevated transaminase levels and to determine the aetiology of elevated transaminase levels in this patient group. Design. Prospective observational study. Setting. Twenty-two-bed Paediatric Intensive Care Unit. Patients. Forty-eight ventilated children with RSV-positive LRTI. Measurements and results. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured daily. In patients with elevated transaminase levels infection with the following viruses was investigated: hepatitis A, B and C viruses, cytomegalovirus, Epstein Barr virus, adenovirus, influenza virus, and parainfluenza viruses (types I, II, and III). Elevated transaminase levels were detected in 22 (46%) patients. The duration of mechanical ventilation (geometric mean; 95% CI) was significantly (P<0.05) longer in the group with elevated transaminase levels: 10.6 (9.4; 11.7) days versus 3.5 (2.8; 4.2) days. This difference remained significant in patients without congenital heart disease. Inotrope use was more common and all deaths occurred in the group with elevated transaminase levels (P<0.05). All patients who died and all but two patients with inotrope requirements had underlying congenital heart disease. One patient with elevated transaminase levels had a simultaneous infection with influenza A virus. Conclusions. RSV disease in ventilated children was more severe if transaminase levels were elevated. Transaminase level elevation was due to hepatitis in the majority of patients. In patients with congenital heart disease we also detected myocardial involvement.