To investigate the mechanisms underlying the increased number of mast cells in autoimmune mice, the proliferative response of autoimmune mast cells to cytokines was examined. Bone marrow cells from autoimmune NZB mice produced scarcely any bone marrow derived mast cells (BMMCs) in the presence of interleukin 3 (IL-3), but were able to generate BMMCs when cultured with pokeweed mitogen-stimulated spleen cell conditioned medium (PWM-SCM). In contrast, NZB BMMCs showed very little proliferation in the presence of PWM-SCM, but proliferated strongly when cultured with stem cell factor (SCF). Non-autoimmune NZW BMMCs showed a strong proliferative response to both IL-3 and PWM-SCM, but proliferated weakly in culture with SCF. Autoimmune NZB x NZW F1 (B/W) BMMCs shared the proliferative activities of both NZB and NZW BMMCs, showing strong proliferation in response to IL-3, PWM-SCM and SCF. All strains (including other non-autoimmune strains) except for NZW demonstrated synergism between PWM-SCM and SCF. This study suggests that the strong proliferative response of autoimmune mast cells to SCF plays a major role in, and that other cytokines are partially responsible for, increasing the number of mast cells in autoimmune mice. These mechanisms are discussed in relation to both constitutive and inducible hematopoiesis.