The human recombinant HLA-DRB1 gene probe was used for histocompatibility typing of two families of beagles for the DLA-D equivalent by using restriction fragment length polymorphisms (RFLP). This method was able to determine the segregation of these genes from the parental animals to the individual F1 offspring. Mixed lymphocyte culture (MLC) reactivity as well as serological typing for class I histocompatibility antigens were also performed for comparison. It was found that there was a high correlation between these three methods. We therefore conclude that RFLP typing is an effective procedure for predicting MLC reactivity in dogs and propose that it is a suitable genotyping method for assignment of class II antigen compatibility for donor-recipient pairs in conjunction with organ transplant studies.