Variants of encephalomyocarditis virus (EMCV), which are immunologically indistinguishable by hyperimmune serum, produce different disease syndromes in mice. For instance, in ICR Swiss male mice, EMCV‐B produces no overt illness, EMCV‐MM produces severe neurological signs followed by death, EMCV‐D destroys pancreatic beta cells producing a disease syndrome resembling insulin‐dependent diabetes mellitus, and EMCV‐K is lethal but produces no overt signs of infection. The present study was done to determine the tissue tropism and histopathology of each of these EMCV variants in the ICR Swiss mouse model. The data show the highest concentrations in the following organs: EMCV‐D in the pancreas, EMCV‐B in the pancreas, EMCV‐MM in the cerebrum, and EMCV‐K in the medulla/brainstem. They also show that the pathological lesions produced by each variant correlate well with viral titers.