Sera from patients with leukemia, lymphomas or other diseases were tested for their capacity to induce differentiation in colonies produced in semi-solid agar by the mouse myelomonocytic leukemia, WEHI-3B. Of 949 samples tested, higher than normal differentiating activity was detected in patients with infections (31% of sera tested) and with acute myeloid leukemia in relapse (35% of sera tested). The higher activity of the latter sera was correlated with the concurrent presence of infections in the relapse leukemic patients. Elevated differentiating activity was also observed in sera from patients with neutrophil levels below 1,000/microliter even if infections were not present. The study indicates that patients with acute myeloid leukemia are able to elevate serum differentiating activity in response to infections or neutropenia and that the serum differentiating factors could play a role in suppressing myeloid leukemic populations by enforcing differentiation in the leukemic cells.