Summary:Several 5‐halopyrimidinones have been shown to have many different biological activities. These include interferon induction, antitumor effects, modulation of immune responses, and polyclonal B‐cell activation. The present study was carried out to determine the effects of treatment of mice with two 5‐halopyrimidinones, 2‐amino‐5‐bromo‐6‐phenyl‐4(3H)‐pyrimidinone (ABPP) and 2‐amino‐5‐iodo‐6‐phenyl‐4(3H)‐pyrimidinone (AIPP), on the murine cytochrome P‐450 system. Administration of ABPP or AIPP to mice by a dosage regimen similar to that resulting in interferon induction by these chemicals resulted in a significant depression in liver cytochrome P‐450 levels. These results suggest that 5‐halopyrimidinones can depress cytochrome P‐450 levels and that this depression may affect the metabolism of other drugs by cytochrome P‐450.