Previously, an association between multiple sclerosis (MS) and HLA-DPw4 has been reported in Scandinavians. In the present study, the distribution of HLA-DP antigens was studied in 34 Japanese MS patients, all of whom fulfilled the criteria for definite MS. HLA-DP typings for DPw1 through w6 and the local specificity, CDP-HEI, were performed using the primed lymphocyte typing (PLT) technique. In addition, the patients were typed for a DR2+, Dw2+/Dw12- related, PLT defined specificity. The distribution of DPw1-w5 in 121 healthy, unrelated Japanese controls were from Nishimura et al., 1984; Nishimura, personal communication). Sera from all 34 patients and 38 controls (both from the HTLV-1 nonendemic, Kyoto region) were examined for the presence of HTLV-1 reacting antibodies by a highly sensitive radioimmuno assay (RIA) using two sources of HTLV-1 antigens, namely total crude protein preparations from disrupted HTLV-1 virions and affinity purified p24 HTLV-1 core proteins. The frequency of DPw4 was significantly increased to 35.3% in Japanese MS patients compared to 16.5% in controls (Relative Risk, RR = 2.8, p = 1.9 x 10(-2)). 41.6% of the MS patients gave clear typing responses with a PLT reagent which recognized a Dw2+ related specificity, which is higher than the frequency of Dw2 (6.8%) in Japanese. Fourteen of the 34 patient sera contrasting to none of the sera from 38 controls contained antibodies of IgG and/or IgM subclasses reacting with the HTLV-1 derived antigens. This difference is highly significant (P less than 1 x 10(-5)).(ABSTRACT TRUNCATED AT 250 WORDS)