Gp160 expressed in vaccinia and produced in vero cells was integrated into iscoms. Gp160 iscoms elicited a high serum antibody response in mice, and after two immunizations a ceiling was reached. The serum antibody response was dissected by the use of defined recombinant DNA products, representing different regions of the gp160 molecule. High antibody titers to the peptid RP135 (a.a. 296-332) correlated with induction of neutralizing serum antibodies. In some animals, gp160 (IIIB) iscoms elicited cross-neutralizing antibodies that also neutralized the distantly related RF isolate.