Previous observations showing the presence in the serum of a component capable of regulating prostanoid biosynthesis in human cultured monocytes, have led us to suspect its presence in human platelets. We have purified this serum monocytotropic factor (SMF) and have shown its identity with a component of platelet membranes. Surprisingly its structure appeared to be very similar to that of a polypeptide growth factor never before identified in platelets: the colony stimulating factor-1 (CSF-1 or M-CSF). Here we show that SMF and CSF-1 have very similar biological properties. Thus, CSF-1 when released from human platelets is capable of triggering the differentiation pathway leading from blood monocytes to resident macrophages. It is likely that cycloxygenase induction plays a pivotal role in these events.