Following the initial description of natural C5 deficiency in inbred mice, a growing number of complement component deficiencies in animals have been described, caused by a variety of genetic defects. Studies on such animals have contributed greatly to an understanding of the specific roles of classical, alternative and terminal pathway activation and inhibition in many infectious and inflammatory diseases. Further investigations in the more recently described models, in combination with the use of genetically engineered knockout mice (with targeted disruption of individual complement components and inhibitors), should continue to provide a fertile source of information regarding the role of complement in such experimental situations. This information is likely to have significant therapeutic implications for human disease.