Transient erythroblastopenia of childhood (TEC) is a pure red cell aplasia which primarily affects children in the infant and toddler age group. The clinical syndrome of TEC is well defined and is characterized by moderate to severe anemia with reticulocytopenia, selective aplasia of the erythroid bone marrow elements, and spontaneous recovery, usually within a month of presentation. We utilized the plasma clot tissue culture technique to explore the defect of erythropoiesis in seven patients with TEC. Culture of bone marrow at diagnosis in four patients revealed an increased erythroid proliferative capacity in one and a decreased capacity in three. The former patient plus three additional patients were found to have a transient serum inhibitor of erythroid colony formation in autologous and allogeneic systems. The three patients with diminished erythroid proliferative capacity had no demonstrable serum inhibitor, and in one patient studied the erythroid proliferative capacity became supernormal after recovery. We conclude that although TEC has a characteristic clinical picture, in vitro studies reveal a variable expression of the erythropoietic defect and support the hypothesis of a heterogeneous pathogenesis of this disorder.