A positive correlation was found between genetic predisposition to diabetes in the mouse and susceptibility to group B Coxsackie virus in this host. Male mice of the inbred strain C57BL/Ks and the following genetic variants were used; mice homozygous for the autosomal recessive gene for diabetes (db/db), the phenotypically normal heterozygous (db/+), and the normal mice which lacked the diabetic gene (+/+). The mortality response of the +/+ mice to intraperitoneal inoculation with Coxsackie virus B4 differed from the response of the two genetic variants (db/db and db/+) derived from this strain. The db/+ variant was more susceptible to Coxsackie virus B4 than the parental background strain (+/+). The db/db variant was more susceptible than either of the other genotypes. Pathological findings of the pancreas of the three genotypes during the acute stage of infection closely paralleled the genotypically dependent susceptibility of the host.