Investigations on the morphology of cells that participate in immune responses in vitro have been limited because the recovery and identification of immunocompetent cells growing dispersely in conventional liquid cultures are technically difficult and allow only the observation of individual antibody-forming cells. Here we used a system in which focal proliferation of antisheep erythrocyte antibody-secreting cells has been induced in semisolid cultures of peripheral blood mononuclear cells. By this method, intact colonies can be observed by light microscopy at the center of each hemolytic area and then processed for electron microscopy without disrupting the connections existing among the cells. Two types of colonies develop: type I colonies which grow deeply into the agar and contain cells that undergo a complete process of differentiation from blast to mature plasma cell, and type II colonies which grow more superficially and do not seem to be directly involved in antibody production.