B1 cells are a subset of B lymphocytes found in many spectes and are implicated in the development of autoimmunity. B1 cells have previously been shown to be suppressed by the T helper (Th)1 cytokine interferon (IFN)‐γ, and to be stimulated by the Th2 cytokines interleukin (IL)‐2, IL‐4, IL‐5 and IL‐10. To examine further the interactions of B1 cells and Th1 cells, we have now tested the effects of the Th1 cell‐inducing cytokine IL‐12 on murine B1 cells. BALB/c mice were immunized with phosphorylcholine conjugated to keyhole limpet hemocyanin (PC‐KLH) and simultaneously treated with 1 μg recombinant murine IL‐12 for 3 consecutive days. In addition to altering the isotype and idiotype distribution of anti‐PC antibodies, IL‐12 treatment was found to cause a loss of peritoneal, but not splenic B lymphocytes in immunized mice. B cell depletion required exposure to IL‐12 plus antigenic stimulation. Levels of peritoneal B lymphocytes were fully restored by day 45, but the majority of these cells belonged to the B2 subset. Additionally, proliferation of B1 cells in vitro induced by IL‐5 was substantially inhibited by IL‐12. IL‐12 itself had no effect on viable cell recovery of peritoneal cells (PeC) cultured in vitro, but viable cell recovery was significantly decreased in PeC cultured with IL‐5 plus IL‐12. These results show that IL‐12 causes the loss of murine peritoneal B1 cells and suggest that treatment with this cytokine may be useful for disease conditions that involve B1 cell dysfunction.