We have previously found that dimethyl sulfoxide (DMSO), a known inducer of differentiation in several kinds of myeloid cells, arrests proliferation of human lymphoid cells including Raji and Akata Burkitt's lymphoma cells at the G1 phase. We investigated whether DMSO affects cell proliferation and differentiation of the lymphoid cell line SKW6-CL4, which is capable of differentiating terminally into IgM-producing cells. As in the case of Raji, Akata, and Molt-4, the proliferation of SKW6-CL4 was reversibly arrested at the G1 phase by treatment with 2% DMSO for 5 days even in the presence of interleukin-6 (IL-6). DMSO inhibited spontaneous IgM secretion as well as IL-6-induced IgM production in SKW6-CL4 at a concentration lower than that affecting cell proliferation. Of the cell-surface differentiation markers CD10, CD20, CD21, and CD23, the expression of CD20 was suppressed by DMSO treatment, and partial restoration of the expression was observed 24 to 48 h after release from DMSO. The level of IL-6 receptor protein was not affected by DMSO treatment. These results indicate that DMSO not only arrests the cell cycle of a human lymphoid cell line SKW6-CL4 at the G1 phase but also inhibits the differentiation into IgM-secreting cells at a concentration lower than that affecting cell proliferation and that DMSO overcomes the effect of IL-6 on terminal differentiation of SKW6-CL4. As a whole, proliferation of human lymphoblastoid cell lines was revealed to be reversibly arrested at the G1 phase by DMSO, which is known to induce differentiation in several myeloid cells, without inducing cell differentiation.