We investigated the effect of recombinant human interleukin-11 (rhIL- 11) on human megakaryocytopoiesis. Nonadherent and T-cell-depleted human bone marrow (BM) mononuclear cells were cultured in a serum-free agar culture system. rhIL-11 alone did not stimulate the growth of human megakaryocyte colonies. However, when rhIL-11 was combined with optimal or suboptimal doses of rhIL-3, the number and size of the megakaryocyte colonies increased. The same results were obtained when highly purified BM CD34-positive cells were used as target cells. Next, we investigated the effect of rhIL-11 on the ploidy of megakaryocytes. The ploidy distribution of individual cells in megakaryocyte colonies obtained by rhIL-11 in combination with rhIL-3 was significantly shifted towards higher values. Furthermore, when highly purified CD41- positive BM cells were cultured in the presence of rhIL-11, the ploidy distribution was shifted towards higher values. This effect was not suppressed by anti-IL-6 antibody. These results suggest that rhIL-11 acts directly as a megakaryocyte potentiator and may play a role in regulating human megakaryocytopoiesis.