Linkage between MHC (major histocompatibility complex) in man and genes responsible for some C components (C2, C4, Factor B) has been described. In contrast, independent segregation has been established for genetic variants of C3 and C6. We report here linkage studies of two families (CC, MF) with C1r deficiency. The following markers were studied: C1r levels (family CC), HL-A, Factor B and MLC (mixed lymphocyte reactivity). In the family CC, as in family MF, C1r° gene was found to be inherited in a straight-forward Mendelian fashion. Linkage to the HL-A region, suggested by the C1r-deficient homozygote CC which was homozygous for HL-A2,W10, MLC and BfT, was ruled out by the independent segregation of 2,W10;T haplotype from the C1r° gene. MLC studies were consistent with the HL-A and Bf typing. Bf typing enabled the differentiation of two HL-A2,W10 serologically identical HL-A haplotypes, one of which was linked to BfT and the other to BfS.