The evaluation of attenuated vaccines in the simian immunodeficiency virus and equine infectious anemia virus animal models has demonstrated the ability of this immunization strategy to elicit broad and enduring immune protection from virus exposure. The development of protective immunity by these attenuated virus vaccines, however, has been shown to be time dependent and to be associated with a complex and lengthy maturation of immune responses over the first 6 to 8 months postinoculation. During this time period, envelope-specific antibody responses undergo an evolution in quantitative and qualitative properties that is similar, but distinct for each lentivirus system. The completed maturation of immune responses is then characterized by relatively steady-state antibody responses that are maintained indefinitely. The accomplishment of optimum vaccine protection is associated with achievement of a fully mature immune response, whereas nonprotective or enhancing vaccine immunity appears to be associated with immature immune responses elicited by ineffective vaccines. These observations indicate that the development of an effective acquired immunodeficiency syndrome (AIDS) vaccine will require immunization strategies that can achieve the necessary maturation of immune responses to human immunodeficiency virus type 1 (HIV-1) antigens in the minimum amount of time. Therefore, AIDS vaccine strategies based on attenuated live virus vaccines or on DNA immunization procedures, perhaps in conjunction with cytokine or secondary costimulatory molecules to accelerate immune maturation, may be best suited to accomplish the goal of an effective and practical AIDS vaccine for worldwide use.