The Chediak-Higashi syndrome (CHS) has been reported in man, cattle, mink, and mice. CHS humans and cattle have an increased incidence of pyogenic infections, whereas CHS mink are more susceptible to Aleutian disease. Age- and sex-matched groups of CHS mice (mutant strain) and C57 Bl/6N (parent strain) were challenged with Candida albicans, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus intravenously and Streptococcus pneumoniae intraperitoneally. A significant increase (P < 0.001) in mortality rate for the CHS mice was demonstrated with all five challenge organisms. Heterozygous mice challenged with C. albicans had a mortality rate essentially the same as C57 Bl/6N mice. The serum immunoglobulin concentrations of CHS mice were found to be the same or greater than the control or heterozygous mice. CHS mice have an increased susceptibility to pyogenic infections, which is not due to immunoglobulin deficiency. These mice may provide a useful laboratory model for the study of increased susceptibility to infection.