Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I (HTLV-I). Although the mechanisms of the leukemogenic process are unknown, the tax gene may have a role in this process. Because clustering occurs with HTLV-Iand ATL, members of ATLfamilies were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors. Toinvestigate the antibody response to this protein, a plasmid, pBHX-4, was constructed to express a recombinant tax protein (r-tax). For ATL patients and their HTLV-I antibody- positive blood relatives, the rate of seroreactivity with the r-tax protein was 67.3% (35/52), compared with 51.6%(97/188)for HTLV-Iantibody-positive control blood donors (P < .05). The difference between direct offspring of ATL patients and matched HTLV-Iblood donors was even greater (84.2% [16/19] vs. 44.2%[42/95]; P <.005). Thus, tax antibody positivity in direct offspring of ATL patients may reflect differences in time or route of HTLV-I infection. Alternatively, it might reflect genetic differences in host susceptibility or virus strain.