MOST LABORATORY ANIMALS have one or more organ system so frequently diseased as to seriously restrict the usefulness of the species for research purposes. In the rat, this distinction clearly belongs to the respiratory system. In the mouse, the respiratory system is only one of several strong contenders. A major problem in using either species is attributed to so-called chronic respiratory disease (CRD), a serious contagious syndrome that remains ubiquitous in distribution and of uncertain etiology despite efforts ofmany in-vestigators over the past four decades. It is perhaps presumptuous to even hope that such a complex and baffling problem as murine CRD can be dealt with adequately in a single paper. Nevertheless, this presentation will attempt to do the following:(1) definethe clinicopathologic entity known as CRD and briefly review the present understanding of its natural history,(2) discuss its significance as a complication of animal research,(3) review the literature concerning the significance of research complications due to Mycoplasma spp in rats and mice, and (4) summarize a series of previously unreported experiments from our own laboratory that give strong support to the view that Myco-pklsma pulmonis alone is capable of causing the syndrome of CRD in the rat and probably is the agent primarily responsible for the naturally occurring disease.