Four biochemically distinct antigen-nonspecific factors have been shown to augment the antibody response to particulate thymic-dependent antigens, i.e., heterologous erythrocytes. These factors are the lymphokines colony-stimulating factor, T cell-replacing factor, and interleukin 2, as well as the monocyte product interleukin 1. The immunoenhancing role of each of these factors in the antibody response is reviewed. A description of the biochemical properties of each factor, the biochemical separation of each factor from other helper factors, the separation of certain factors using different producing cells, and a description of the culture systems used to demonstrate helper activity are included. Questions concerning the target cell specificity and hence the mechanism of action of each factor are raised. Finally, recent data from several laboratories demonstrating the synergistic interactions of the helper factors in enhancing antibody synthesis are reviewed and models of B cell activation are presented.