Out of 153 newly referred human T-lymphotropic virus type I infected patients, 42 (27%) had 5% or more abnormal lymphocytes, consistent with the diagnosis of smoldering adult T-cell leukemia/lymphoma. The abnormal lymphocyte percentage was higher in patients with human T-lymphotropic virus type I associated inflammatory disease compared with asymptomatic carriers (P=0.006). Over 4.5 years median follow up, 4 patients, all with 10 or more human T-lymphotropic virus type I DNA copies/100 peripheral blood mononuclear cells at presentation, but only one with 5% or more abnormal lymphocytes at presentation, developed adult T-cell leukemia/lymphoma. Thus, high pre-morbid human T-lymphotropic virus type I proviral load, rather than fulfilment of the classification criteria for smoldering adult T-cell leukemia/lymphoma, was associated with an increased risk of developing aggressive adult T-cell leukemia/lymphoma.