The presence of circulating "flower cells" and a low prevalence of antibody to Tax regulatory protein of human T-lymphotropic virus type I (HTLV-I) are characteristics of adult T-cell leukemia (ATL). To examine the predictability of levels of HTLV-I antibodies and of flower cell-like abnormal lymphocytes (Ably) for the risk of ATL among asymptomatic HTLV-I carriers, we prospectively evaluated the levels of viral markers of five HTLV-I carriers who developed ATL and 38 age-, sex-, and screen-matched HTLV-I-positive controls in the Miyazaki Cohort Study. After accounting for matching factors, Ably level was slightly, but not significantly, higher among cases than among controls (P =.13). Anti-HTLV-I (odds ratio [OR] = 1.6 per twofold dilution; 95% confidence interval [CI] 0.94, 3.8) was associated with ATL diagnosis, but antibody to Tax regulatory protein (anti-Tax) was not (OR = 0.78; 95% CI 0.26, 1.7). Anti-Tax level was low for all ATL cases for up to 10 years preceding their diagnosis, independent of the level of anti-HTLV-I titer. HTLV-I carriers with a higher anti-HTLV-I titer and a lower anti-Tax reactivity may be at greatest risk of ATL.