Enriched populations of Ia+ Fc receptor-negative dendritic cells were compared to other cell types for their stimulatory activity in primary mixed lymphocyte reactions to alloantigens and 2,4,6,-trinitrophenylated syngeneic cells. Dendritic cells were 20-100 times more effective than unfractionated splenocytes. A second cell type exhibiting strong stimulatory activity was an Ia+ Fc receptor-positive transiently adherent cell. Both types of stimulatory cells were only effective when able to produce the monokine interleukin 1. Thus glutaraldehyde-fixed cells were not stimulatory unless extraneous interleukin 1 was added. Stimulation of helper cells by either dendritic cells or Ia+ Fc receptor-positive cells resulted in the production of interleukin 2. The data are discussed in view of the recently formulated interleukin model as a minimal scheme to explain T-T cell interactions during the in vitro induction of cytotoxic T lymphocytes.