Association between HLA and multiple sclerosis (MS) was investigated at the population level on 100 MS patients genotyped for HLA-A, B, C, DR and Bf, Glo, and on 155 patients phenotyped for the same HLA antigens. Association between MS and DR2 was clearly confirmed, although its strength is rather weak. No other genetic marker could be related to the disease, no haplotype nor any allelic combination could be recognized as MS specific, and antigen genotype frequencies among the diseased could not ascertain the mode of inheritance, although dominance is very likely. Computer analysis between HLA, Bf, Glo and age of the patient, sex, age of onset and evolution of MS, impairment indexes, titres of anti-DNA and anti-measles antibodies in CSF did not show any interaction. Twenty sib pairs and two trios of MS were also studied; they showed no significant distortion with the random distribution of haplotypes. DR2 gene frequency, however, was significantly higher in sib pairs showing one or two haplotypes than in HLA different affected siblings. Three crossing-overs were identified which suggest where the HLA-linked MS susceptibility (MSS) gene could be located within the HLA segment, while other epistatic MSS genes or environmental factors are likely to be important.