A gene product (p42) of the long open reading frame, now termed tax, of the viral genome of human T-cell leukemia virus type 1 (HTLV-1) may be related to the transformation of T cells in adult T-cell leukemia-lymphoma (ATLL). To evaluate its association with the disease, we compared the prevalence of antibody to p42 in sera obtained from 105 HTLV-1 carriers and 64 ATLL patients from southwest Japan. The prevalence of the anti-p42 antibody reactivity was 63% among carriers and 31% among cases. The cases were more than 3 times as likely to lack antibody to p42 than carriers, the relative odds (OR) = 3.4, p = 0.001. When the samples were tested for antibody against p24, the most immunogenic core protein, the prevalence was somewhat higher among carriers (65%) than in cases (52%), but not significantly so (p = 0.15). Among the healthy carriers, the correlation between the prevalence of both antibodies was high (p = 0.001), and only 25% of those who had antibody to p24 lacked antibody to p42. However, among the cases, reactivity to both antigens was independent (p = 0.52), and 65% of those with antibody to p24 lacked antibody to p42, OR = 6.3, p = 0.0004. Thus the strongest serologic marker of ATLL following diagnosis was lack of reactivity to p42, particularly among those subjects with anti-p24. Whether this altered response is present prior to disease remains to be determined.