Severe combined immunodeficient (scid) mice are valuable animals to study a variety of physiologic and disease processes. Their capacity to support multiple tissue xenografts permits these mice to be used as intermediate models for host-specific, fastidious organisms for which a small animal model has not been available previously. However, because they are unable to mount a normal immune response, they are very susceptible to a variety of primary and opportunistic microbial pathogens. Fatal, naturally occurring infections with bacteria such as Proteus mirabilis, Streptococcus viridans, and Escherichia coli have been observed. In addition, based on observations after experimental or naturally occurring viral infections, scid and scid/beige mice have been shown to be very susceptible to infections with viruses such as mouse hepatitis virus, Sendai virus, and murine respiratory virus, with resulting mortality. Of the parasitic infections, Pneumocystis carinii is a relatively common contaminant of the respiratory tracts of scid mice and may complicate research projects, particularly experimental respiratory tract infections. In view of the enhanced susceptibility of these mice to infections of this type, it is essential that they be housed under optimal conditions, which include implementing stringent management practices and a functional barrier system.