Human peripheral blood monocytes were cultured under conditions which prevent macrophage development. Media containing selected charges of fetal calf serum as well as a number of serum-free and protein-free media were found to convert monocytes into homogenous populations of loosely adherent veiled cells. After one week of culture, these cells developed dendritiform elongations. Functionally, these cells acquired an increased capability of serving as accessory cells in T lymphocyte mitogenic stimulation. Phenotypically, they were strongly reduced in macrophage markers such as nonspecific esterase, phagocytosis and Fc-receptors. The majority of the population was even negative for these markers. It thus appears that highly active accessory cells, which closely approach the phenotype of lymphoid dendritic cells, could be deduced from monocytes. These accessory cells could be maintained in culture for several weeks without proliferation and without converting to macrophages. They could further be induced to differentiate to macrophages by an activity present in human serum. Ontogenetically, the accessory state as described here is a differentiation stage preceding macrophage differentiation. When macrophages differentiate from monocytes, they have to pass the transient stage of increased accessory activity.