We have compared two types of plasmids for DNA immunization against HTLV-I envelope glycoproteins. One type of plasmid contains the coding DNA of the complete envelope gene of HTLV-I under the control of the CMV promoter with (CMVenvLTR) or without (CMVenv) the tax/rex genes. The second type contains the coding DNA of the complete env gene of HTLV-I under the control of the human desmin muscle specific promoter (DesEnv). These plasmids were inoculated into mice and the humoral response was studied by flow cytometry, ELISA and neutralization assays. Inoculation of the DesEnv construct elicited a higher humoral response with better neutralization properties than the injection of CMVenvLTR or CMVenv plasmids. The choice of vectors will be important for the design of genetic HTLV-I vaccines.