Background: 15‐deoxy Δ‐ 12,14 ‐prostaglandin J 2 (15d‐PGJ 2 ) is an endogenous ligand of peroxisome proliferator‐activator receptorγ (PPARγ ). Treatment of some B cell lymphomas with 15d‐PGJ 2 increases oxidative stress and induces apoptosis. HO‐1 is an oxidative stress‐inducible enzyme but its expression in human B cell lymphomas is unknown. We hypothesized that PPAR ligands induce HO‐1 in malignant B cells. Methods: Ramos and Granta B cell lymphoma cells and 8226 multiple myeloma cells were treated with 15d‐PGJ 2 . HO‐1 protein expression was assessed by western blot. Markers of oxidative stress included mitochondrial superoxide production and generation of reactive oxygen species (ROS). Results: Treatment of Ramos cells with 15d‐PGJ 2 strongly increased ROS and mitochondrial superoxide production and significantly reduced cell viability. Granta and 8226 cells had a similar response to 15d‐PGJ 2 treatment but they exhibited a concentration‐ and time‐dependent increase of HO‐1 expression. Interestingly, Ramos B cells did not up‐regulate HO‐1. Conclusions: The PPARγ ligand 15d‐PGJ 2 induces cell death in some B malignant cell lines and differentially regulates the induction of HO‐1. This suggests that malignant B cells have different anti‐oxidant defense mechanisms. Research supported by DE011390, ES01247, The Leukemia and Lymphoma Society and the Lymphoma Research Foundation.