The production of colony-stimulating factor (CSF) by the peripheral blood cells of untreated patients with acute myeloid leukemia (AML) was measured in the agar culture system using normal human bone marrow as the source of colony-forming units (CFUc). CSF production was variable and was related to the morphologic subtype of AML, cells from patients with monocytic leukemia produced normal or large quantities of CSF, while (with 1 exception) those from patients with myeloblastic leukemia produced little or no CSF. There was a general relationship between CSF production and serum lysozyme levels. Attempts to demonstrate a consistent inhibitory effect exerted by leukemic peripheral blood cells on normal leukopoiesis in vitro were negative. The addition to the feeder layer of cells from patients with monocytic leukemia apparently could raise CSF levels above those obtained with normal peripheral blood leukocytes alone, possibly by recruiting additional CFUc from normal marrow.