Pluripotent hemopoietic progenitors (CFU-GEMM) give rise to multilineage hemopoietic colonies in culture. We have examined the erythropoietin requirements of CFU-GEMM-derived erythroid progeny in patients with polycythemia vera (PV) and studied their proliferative activity by short-term exposure to 3HTdR. Mixed colonies with erythroid components were observed in all bone marrow and peripheral blood samples from patients with PV that were cultured without addition of exogenous erythropoietin. This response is consistent with previously reported growth patterns for CFU-E and BFU-E. The frequency of mixed colonies increased regularly when erythropoietin was added to the cultures. Short-term exposure of peripheral blood specimens to 3HTdR prior to plating yielded a reduction of the plating efficiency by 20%-70% when compared to cells that were not exposed to 3HTdR. The observation of cycling CFU-GEMM in PV contrasts with the usually quiescent behavior of CFU-GEMM in peripheral blood of normal individuals under steady-state conditions. These results support the view that the increased proliferative rate observed for CFU-GEMM may be responsible for the increased formation of blood cells in PV.