Abnormally large lymphocytes with Pelger-like nuclear lobulation have been found in peripheral blood of smoldering adult T-cell leukemia-lymphoma (ATL) patients. They are also found in quite low percentage in peripheral blood of healthy HTLV carriers. Therefore, it has become difficult to discriminate smoldering ATL having only abnormal lymphocytes from a healthy human T-cell leukemia virus (HTLV) carrier only by morphology and serology. We found that patients with smoldering ATL with visceral organ involvement such as skin or lung lesions had much higher titer (about 1 : 1,000) of anti-HTLV antibodies than those with other subtypes of ATL (about 1 : 250); the difference was highly significant (p less than 0.001). In addition, the period of survival of patients with smoldering ATL having antibody with high titer was much longer than that of patients with other subtypes of ATL, suggesting the role of a host immune response. Four cases of HTLV-negative ATL were found to have the same chromosomal abnormality as that has been seen in HTLV-positive typical ATL; the situation was quite similar to Burkitt's lymphoma. Since it has been considered that HTLV does not include oncogenes, a common oncogenic mechanism, ATL specific cellular oncogenes, might exist: they might be activated by HTLV or a mechanism other than a virus.