There are two distinct receptors identified for opsonic fragments of C3 on human phagocytic cells designated CR1 and CR3. Using monoclonal anti-receptor antibodies developed in this laboratory we demonstrated that both receptors rapidly augment their expression in response to a variety of biological agents including: the chemotactic peptides, fmet-leu-phe, C5a; phorbol myristate acetate; leukotriene B4; a Raji cell derived lymphokine; and the calcium ionophore, A23187. We have further shown that this process is dependent upon extracellular calcium, calmodulin and a functional microtubule system. De novo protein synthesis is not required. We further showed that the intracellular pool of CR3 cosediments with specific granules when disrupted neutrophils are fractionated on sucrose gradients. Moreover, organelle depleted neutrophil cytoplasts as well as neutrophils obtained from a patient lacking specific granules are unable to upmodulate receptor expression. The importance of these studies is underscored by the description of a new clinical syndrome marked by recurrent infections. These individuals lack CR3 and their cells exhibit a variety of functional defects. In addition it has been recently shown that patients with systemic lupus erythematosus have a decreased expression of CR1 on their erythrocytes. Studies are underway to more fully understand the function of these receptors in health and disease.