Exposure of piglets to 68-72 h of hyperoxia has previously been shown to blunt hypoxic pulmonary vasoconstriction (HPV). We tested the hypothesis that the administration of a scavenger of toxic oxygen radicals during exposure to hyperoxia would preserve HPV in piglets. Newborn piglets were kept in FIO2 greater than 0.90 for 68-72 h and compared to control animals kept in room air. Randomly selected animals from both groups were given the O2 metabolite scavenger, dimethylthiourea (DMTU) (500 mg/kg followed by 250 mg/kg/d), resulting in plasma levels of 2-6 mM. Following the oxygen or room air (RA) exposure period, piglets had pulmonary vascular resistance (PVR) measured following a 20 min exposure to alveolar hypoxia (FIO2 = 0.12). Both groups of RA-exposed animals (DMTU and saline treatment) as well as the hyperoxia-exposed saline group had almost 2-fold increases in PVR during exposure to hypoxia (P less than 0.05). Contrary to expectations, the PVR in the hyperoxia-exposed DMTU group did not rise significantly during hypoxia and the use of DMTU did not restore HPV by increasing PVR to levels greater than the hyperoxia/saline group (P = 0.70). Therefore DMTU does not appear to prevent hyperoxia-induced blunting of HPV in piglets.