Mycoplasmas are a heterogenous group of prokaryotic organisms causing a wide variety of diseases, including autoimmune disorders. Thus, it is not surprising that various mycoplasmas strains, including Mycoplasma arginini, M. arthritidis, M. neurolyticum and M. pulmonis, are able to regulate the immune response. Though some of the studies of the immunomodulatory action of mycoplasmas have been done in vivo, the majority of the investigations have been conducted in vitro. This has led to the recognition that mycoplasmas are polyclonal activators of both B and T cells from several species, acting through MHC-restricted or -unrestricted pathways. Mycoplasma activation not only induces T-cell proliferation but also leads but to the formation of cytotoxic T cells. We, as well as others, have shown that mycoplasma-mediated B-cell activation induces proliferation as well as Ig secretion, and also that mycoplasma stimulation of lymphocytes may result in the production of cytokines. We communicate here our investigations into the effects of an M. arginini strain on the growth and maturation of preactivated B cells. After an initial biological characterization of the M. arginini effects in vitro, we established the protein nature of the growth-supporting activity and proceeded further on to isolate and identify the responsible proteins. The use of lipid- and lipoglycan-free extracts has allowed us to further extend our studies on the biological activities of the proteins from M. arginini and to compare these results with the effects obtained using live organisms. Furthermore, the study was extended to include a characterization of the in vivo-induced effects of live M. arginini. Altogether, the results from these experiments allow us to conclude that M. arginini is a T-cell independent polyclonal B-cell mitogen, mediated by five identified proteins, inducing growth and Ig secretion of both resting and preactivated B cells.