The interaction of human immunodeficiency virus (HIV)-derived vectors with wild-type virus was analyzed in transduced cells. Vector transcripts upregulated by infection had no measurable effect on HIV type 1 (HIV-1) expression but competed efficiently for encapsidation, inhibiting the infectivity and spread of HIV-1 in culture and leading to mobilization and recombination of the vector. These effects were abrogated with a self-inactivating vector.