1 To investigate the e ect of moderate hypoxia alone or combined with an in¯ammatory reaction or after 3-methylcholanthrene (3MC) pre-treatment on cytochrome P450 (P450), conscious rabbits were exposed for 24 h to a fractional concentration of inspired O 2 of 10% (mean PaO 2 of 34 mmHg). Hypoxia decreased theophylline metabolic clearance (Cl M ) from 1.73+0.43 to 1.48+0.13 ml min 71 kg 71 (P50.05), and reduced (P50.05) the formation clearance of theophylline metabolites, 3-methylxanthine (3MX), 1-methyluric acid (1MU) and 1,3-dimethyluric acid (1,3DMU). Hypoxia reduced the amount of CYP1A1 and 1A2 but increased CYP3A6 proteins. 2 Turpentine-induced in¯ammatory reaction reduced (P50.05) the formation clearance of 3MX, 1MU, and 1,3DMU, and diminished the amount of CYP1A1, 1A2 and 3A6 proteins. However, when combined with hypoxia, in¯ammation partially prevented the decrease in Cl M , especially by impeding the reduction of 1,3DMU. The amount of CYP1A1 and 1A2 remained reduced but the amount of CYP3A6 protein returned to normal values. 3 Pre-treatment with 3MC augmented the Cl M by 114% (P50.05) due to the increase in the formation clearance of 3MX, 1MU and 1,3DMU. 3MC treatment increased the amount of CYP1A1 and 1A2 proteins. Pre-treatment with 3MC prevented the hypoxia-induced decrease in amount and activity of the P450. 4 It is concluded that acute moderate hypoxia and an in¯ammatory reaction individually reduce the amount and activity of selected apoproteins of the P450. However, the combination of hypoxia and the in¯ammatory reaction restores P450 activity to near normal values. On the other hand, pretreatment with 3MC prevents the hypoxia-induced depression of the P450.