Two distinct diseases, adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), develop in a minor population of HTLV-1 carriers. We examined the relationship between the viral genome dose in the peripheral-blood mononuclear cells and the serological response in HTLV-1 carriers and patients with HAM/TSP. The antibody titer to HTLV-1 gag and env proteins, as well as the frequency of an antibody response to viral protein p40tax and the titer, increased with increasing viral genome dose. However, the number of abnormal lymphocytes was not directly related to the host viral load. Patients with HAM/TSP generally showed a higher genome dose than healthy carriers and also had higher antibody titers than healthy carriers with the same HTLV-1 load, supporting the existence of an augmented immune response in these patients. These findings suggest that the antibody titer to HTLV-1 genome products, and not the number of abnormal lymphocytes, intimately reflects the approximate viral load in HTLV-1-infected individuals.