Two DNA constructs encoding portions of the human immunodeficiency virus type-1 (HIV-1) genome have been used to raise antibody responses in BABL/c mice. One DNA (pNL4-3.env) expresses the natural form of the envelope glycoprotein (Env) of HIV-1-NL4-3 (NL4-3). The second (pNL4-3.dpol) produces noninfectious NL4-3 particles. These two DNAs (alone or in combination) raised only transient titers of anti-Env IgG. In the same group in which pNL4-3.dpol DNA raised only transient antibody responses to Env, this DNA raised persistent antibody responses to the p24 virion capsid protein (CA). Antibody responses to Env and CA also showed different abilities to be boosted. The final boosts of pNL4-3.dpol DNA increased titers of anti-CA antibody, but failed to boost the falling titers of anti-Env antibody. At peak titers of anti-Env activity, sera with relatively low ELISA titers of anti-Env IgG (end points of 1:6250) had good titers of neutralizing antibody (approximately 1:3800 for 50 TCID50 of NL4-3). At the end of the experiment (a time when anti-Env antibodies had fallen to near background levels), in vitro-restimulated splenocytes from both pNL4-3.env and pNL4-3.dpol DNA vaccine groups exhibited similar cytotoxic activity.