The dioxin/aryl hydrocarbon (Ah) receptor functions as a ligand-activated transcription factor that mediates toxicity of dioxins and related environmental pollutants. We have developed a transgenic mouse model that expresses a constitutively active Ah receptor. The immune system is one of the most sensitive target organs for dioxin toxicity and we have therefore investigated alterations of different lymphocyte populations in these mice. The population of mature bone-marrow derived B cells was enlarged, consistent with previous findings in dioxin exposed mice. In contrast, the peritoneal population of CD5-expressing B cells (B1 cells) was significantly diminished. This is the first study that demonstrates the effect of an activated Ah receptor on B1 cells. Since these cells are important mediators of innate immunity against pathogens such as Influenza virus, these results may explain the decreased resistance against infections that has been documented after dioxin exposure. (C) 2003 Elsevier Science (USA). All rights reserved.