This review describes a series of studies performed in our laboratory which have focused on the activation and subsequent proliferation and differentiation of human B lymphocytes. Utilizing polyclonal signals which activate B cells by interacting with their surface membrane Ig, we have examined the events in the transition of a resting B lymphocyte to an Ig-secreting cell. A major theme in these studies is the role of soluble factors in B cell proliferation and B cell differentiation. Specific B cell growth and differentiation factors are described. Data on their sources, biochemical characterization, and methods of assay are included. Additionally, the potential role of interleukin 2 in human B cell function is discussed. The recognition that B cells exist in a variety of activation states and that transition between different states is dependent upon different signals was the impetus for a series of studies which more precisely delineated these states and the signals involved. These findings and the observations from other investigators led to a proposed model of the sequential steps in a factor-dependent B cell differentiation pathway. This model is discussed and related to the mechanisms of T cell activation and growth. Finally, the effects of two pharmacologic agents, glucocorticoids and cyclosporin A, on human B cell function are described and discussed in the context of this model.