Nesiritide is a synthetic form of B-type natriuretic peptide. It is approved for the treatment of acute exacerbations of congestive heart failure in hospitalized adult patients. It is currently under investigation for use in other settings and other patient populations. This article describes administration of nesiritide to an infant patient with severe pulmonary hypertension and cor pulmonale. No adverse reactions occurred during administration of the drug. Specifically, there was no hypertension, vomiting, arrhythmia, or changes in renal function. No changes in renal function occurred in the months subsequent to treatment. This case report illustrates that nesiritide can be safely administered to critically ill infants with pulmonary hypertension and cor pulmonale. Our patient experienced a decrease in pulmonary pressure and improved clinical condition during and after the infusion. However, further study is required to fully evaluate the safety and efficacy of nesiritide for these patients.