The risk of perforation during 65 endomyocardial biopsies (380 specimens) was investigated using two different sheaths to guide the biopsy forceps in five heart-transplanted children aged 1.6-12.9 years. One of the sheaths guided the biopsy forceps simply into the right ventricle (prefabricated 110 degrees curved tip); the other (specially curved sheath) had two curves, the distal one of which guided the forceps posteriorly toward the interventricular septum. The position of the sheath was evaluated by biplane fluoroscopy and, in children </=4 years of age, also by transesophageal echocardiography (TEE). Perforation was defined as clinical perforation (chest pain and pericardial effusion as judged by transthoracic echocardiography or TEE) and "near perforation" (epicardial fat in specimens). The prefabricated sheath was associated with 10 incidents of perforation (one clinical and nine near perforations) after 16 biopsies and 96 specimens (10.4%) compared with 2 near perforations after 49 biopsies and 284 specimens (0.7%) after using the specially curved sheath (p < 0.001). We conclude that the risk of perforation during endomyocardial biopsy can be reduced by using a specially curved sheath to guide the biopsy forceps toward the interventricular septum.