Bone marrow and/or peripheral blood cells from 12 patients with acute promyelocytic leukemia (APL) were cultured in soft agar or methylcellulose in the presence of 15% human placental conditioned medium as a source of colony stimulating factor. Buffy coat cells, taken from ten patients when APL was diagnosed, produced a growth pattern in soft agar that was characterized by a high incidence of small, relatively uniform clusters of promyelocytes, which, when stained in situ, reacted strongly with myeloperoxidase, Sudan black B and chloroacetate esterase. In six cases, the leukemic origin of the cluster forming cells was demonstrated by the presence of the t(15;17) in these cells. During periods of complete remission the small clusters were replaced by larger and more diverse aggregates which had a normal karyotype. At relapse the small cluster growth pattern returned. The growth pattern of small clusters is more commonly associated with APL than with other types of acute myeloid leukemia.