The fidelity of DNA strand transfer reactions catalyzed by human immunodeficiency virus type 1 reverse transcriptase has been studied in vitro. A model system involving two sequential DNA strand transfers was developed to simulate the process of forced copy-choice recombination. A propensity for nucleotide misincorporation at the junction of the strand transfer, as determined by DNA sequencing of the reaction products, was found consistent with a model involving the addition of nontemplate-directed nucleotides prior to the transfer of nascent DNA onto the accepting RNA template [Peliska, J. A., & Benkovic, S. J. (1992) Science 258, 1112]. The kinetic and mechanistic factors that may dictate which nucleotide bases are incorporated at recombination sites during strand transfer and the possible consequences of recombination-induced mutagenesis in vivo are discussed.