Through a literature search, we identified a total of 59 nuclear families with Hodgkin's disease (HD). The affected individuals in these families were HLA haplotyped. To evaluate the role of HLA-linked determinants of HD and investigate the mode of inheritance of familial HD, a combined segregation and linkage analysis was performed, together with a semi-parametric analysis of sib pairs. Amongst single locus models, a general single locus model showed no improvement over an additive model. However, a two locus additive model gave the best overall fit and a lod score of 3.55. We conclude that HD is most likely to be determined by both an HLA-associated major gene and other non-HLA genetic factors together with environmental effects.