Human marrow grown in a plasma clot gives rise to discrete colonies of nucleated red cells in response to erythropoietin (EPO). In 10 studies of human marrow with normal erythropoiesis, human EPO in doses up to 1 unit/ml produced a significant increase in colonies when compared to sheep EPO. To achieve 50% of maximum colony growth, only 0.1 units/ml of human EPO was needed in contrast to 0.5 units/ml of sheep EPO. In seven other experiments, nandrolone decanoate, 10(-7) to 10(-9) M, yielded a mean increase in colonies of 38% when compared to cultures without added androgen. This effect was entirely dependent on the presence of EPO. We conclude that the method is useful for the invitro study of factors affecting early events in erythropoiesis.