A full-term, male neonate developed persistent pulmonary hypertension, and responded to high-frequency oscillatory ventilation and inhaled nitric oxide (INO). Discontinuation of INO was attempted three times and was followed by severe desaturations due to right-to-left shunt through the patent ductus arteriosus and patent foramen ovale. As a result of this rebound pulmonary hypertension, the neonate was maintained on INO therapy for 6 days. Successful discontinuation was achieved by using the phosphodiesterase inhibitor, dipyridamole. We speculate that during exogenous INO therapy, endogenous nitric oxide was inhibited, thus cyclic guanosine 3′,5′-monophophate, the smooth muscle relaxant, was rapidly hydrolyzed. By inhibiting phosphodiesterase, smooth muscle relaxation occurred, and consequently weaning from INO was achieved.