The complement cascade is regulated by a series of proteins that inhibit complement convertase activity. These regulatory proteins, most of which possess binding sites for C3b and/or C4b, can be roughly divided into two groups, one that controls inappropriate complement convertase activity on the surface of cells, and another that controls convertase activity on immune complexes in serum. In this review we focus upon the structural and functional comparisons of the CR1 and CR2 proteins of man and mouse. A single gene encodes these proteins in the mouse while the human requires two. The analysis of mice lacking the CR1/CR2 proteins demonstrates the requirement of these proteins for the regulation of complement convertase activity within lymphatic tissue immune complexes that is not efficiently controlled by other membrane bound or serum regulatory proteins.