The induction of specific neutralizing antibodies is an important part of vaccine strategy against human T cell leukemia virus type I (HTLV-I). A recently developed reporter gene induction assay was used to detect and quantify neutralizing antibodies in sera of HTLV-I-infected patients with different clinical states: Most sera (73/89) displayed an inhibitory activity. Neutralizing antibodies were more frequently detected in sera of patients with tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) or sicca syndrome (SS) (100%) than in sera of patients with adult T cell leukemia (ATL; 50%) or of asymptomatic carriers (AS; 83%). The mean titers in the different groups were significantly different (ATL < AS < TSP/HAM and SS). The antibody reactivity detected by the reporter gene inhibition assay was significantly related to the recognition of the neutralizable immunodominant domain (aa 175-199) of the surface envelope glycoprotein, indicating the importance of this region for potential vaccines.