Inhalation of partially ionized oxygen may have less adverse effects on lung functions than medical oxygen. Guinea pigs inhaled air, 100% molecular medical oxygen (O(2)mol), partially negatively (O(2)neg) or positively (O(2)posit) ionized oxygen during 17 and 60 h. After 17 h, dityrosines, markers of oxidative injury, in lung homogenate increased in O(2)neg and decreased in O(2)posit groups vs. controls. After 60 h, dityrosines rose after inhalation of O(2)mol and O(2)neg, but not in the O(2)posit group. Lysine-LPO products increased and lung wet/dry weight ratio decreased in O(2)mol and O(2)neg, and not in O(2)posit group. Relative neutrophil count in BALF was elevated in all oxygen-treated groups with lower numbers in O(2)posit vs.O(2)mol and O(2)neg groups. After 60 h, surfactant activity was better in O(2)posit vs. O(2)mol group. In conclusion, long-term inhalation of partially positively ionized oxygen is associated with less oxidative stress, milder lung inflammatory response, and better surfactant activity than molecular or negatively ionized oxygen.