The effect of killed Corynebacterium parvum vaccine on the course of murine aspergillosis is described. A grid-counting technique was employed to quantitate tissue invasion by Aspergillus nidulans in the brain, heart, and kidneys (the target organs) of normal mice and of mice treated systemically with killed C. parvum vaccine. Simultaneous treatment of mice with C. parvum and A. nidulans significantly increased the mortality rate, in contrast to treatment of mice with C. parvum prior to or following A. nidulans, which had no significant effect on mortality. Fungal invasion of the tissues of the brain and kidneys was significantly increased in mice pretreated or posttreated with C. parvum, but fungal invasion of the heart was not effected by these treatements. Simultaneous treatment of mice with C. parvum and A. nidulans significantly increased fungal invasion of the heart but did not effect tissue invasion of the brain and kidneys. It was concluded that killed C. parvum vaccine reduces host resistance to Aspergillus infection and facilitates the curse of fatal murine aspergillosis. These results suggest further caution in applying systemic C. parvum in the therapy of human neoplasia.