A number of in vitro studies have implicated protein kinase Cdelta (PKCdelta) and PKCepsilon in the regulation of the immune system. In recent years, this has been convincingly demonstrated in mice deficient for PKCdelta and PKCepsilon. The reported phenotypes for these transgenic mice indicate that PKCdelta suppresses immunoresponsiveness and inhibits the proliferation of B-lymphocytes, while PKCepsilon is required for macrophages to mount an effective immune response to bacterial pathogens. In either case, these isoenzymes appear to cooperate in fine-tuning certain immunoreactions by either suppressing (PKCdelta) or stimulating (PKCepsilon) the transcription of various cytokines. This review will compare and contrast the structures of these two nPKC isoenzymes and their respective roles in the modulation of cytokine production and various other cellular processes, such as growth, differentiation, apoptosis, and tumor suppression.