It is determined that the classical HLA sib-pair method can be used for the detection of linkage and determination of mode of inheritance of a disease when applied to non-HLA data, where attention is restricted to that subset of all parental matings that can produce affected sibs where unequivocal determination of haplotype sharing by descent values can be obtained. With the increasing use of restriction fragment length polymorphisms (RFLPs) to detect disease genes, it is predicted that this method will be applicable to many diseases.