Animal models have been widely used to investigate the role of the complement system in a host of infectious and inflammatory diseases. Over the last 30 yr, a number of naturally occurring genetic deficiencies of complement components have been described in different species of laboratory animals. Where genetic studies have been undertaken, all these defects appear to follow an autosomal recessive pattern of inheritance and a number of them have been characterized at the molecular level. This chapter is a review of the complement-deficient strains available, experience derived from the use of such animals in experimental models in vivo, and of how the results of such studies have helped to define the effects of complement deficiency at different stages of the complement pathway.