Abstract: Heme oxygenase is a rate‐limiting enzyme in heme catabolism that cleaves heme to form biliverdin, carbon monoxide, and iron. Heme oxygenase‐1 is an inducible isozyme and is expressed in many types of cells and tissues. Large amounts of these heme degradation products may be noxious to the host, especially in the brain. We therefore searched for the factors that suppress the expression of heme oxygenase‐1. Northern blot analysis showed that treatment with interferon‐γ and with interleukin‐1β for 24 h decreased the expression levels of heme oxygenase‐1 mRNA to ∼20 and ∼50% of the control levels, respectively, in a human glioblastoma cell line, T98G. Treatment with a combination of these two cytokines additively decreased the expression levels of heme oxygenase‐1 mRNA. Western blot analysis showed that the expression level of heme oxygenase‐1 protein was also decreased by treatment with interferon‐γ, but not with interleukin‐1β. Moreover, pretreatment with interferon‐γ partially suppressed the induction of heme oxygenase‐1 mRNA expression caused by either sodium nitroprusside, cadmium, or hemin. These findings raise the possibility that the expression of heme oxygenase‐1 is down‐regulated by interferon‐γ in the nervous system.