Interactions between porcine antigen presenting cells (pAPCs) and host lymphocytes may be important in cellular and humoral rejection of porcine organ xenografts. To investigate the role of pAPCs in the activation of xenogeneic lymphocytes, porcine bone marrow cells were stimulated using porcine GM-CSF with or without porcine IL-4 to generate populations of pAPCs that had phenotypic characteristics of myeloid dendritic cells. These bone marrow-derived pAPCs were weak stimulators of xenogeneic (mouse and human) T cells in vitro but induced primary B-cell proliferation and augmented CD40-induced B-cell proliferation. Inoculation of mice with small numbers of pAPCs resulted in localized expansion of lymph node B cells. The mitogenic effect on xenogeneic B cells could be reproduced by medium in which pAPCs had been cultured, implicating one or more soluble products. In blocking experiments IL-12, IL-6, and IL-10 were found not to contribute to the mitogenic effect of pAPC medium. In contrast, pIFN was found to be capable of augmenting CD40-induced proliferation of xenogeneic B-cell proliferation but did not act as a B-cell mitogen. We conclude that myeloid APCs from the pig produce soluble factors that are capable of acting as primary mitogens for xenogeneic B cells as well as augmenting additional B-cell activating stimuli. This direct interaction between porcine APCs and xenogeneic B cells may serve as an important adjuvant for the stimulation of humoral immunity to porcine xenografts.