As the reverse transcriptase activity of the HIV-1 RT heterodimer catalyzes the synthesis of minus-strand strong stop DNA (-sssDNA), the RNaseH activity of the same RT heterodimer catalyzes the degradation of the complementary viral genomic RNA sequences. Degradation of this RNA is required for the efficient transfer of the -sssDNA to the 5' end of the viral genomic RNA. The RNase H active site is positioned within the HIV-1 RT heterodimer so as to attack the RNA strand of the RNA:DNA duplex at a point 18 bases behind the site of reverse transcription (Furfine and Reardon 1991; Ghosh et al. 1995; Gopalakrishnan et al. 1992; Wohrl and Moelling 1990). The rate of RNase H cleavage is substantially lower than the rate of DNA synthesis, however (Kati et al. 1992), and may further depend on RT stalling and structural features of the viral genomic RNA template. The product of these combined DNA synthesis and RNA degradation events is a DNA strand still duplexed with extended viral genomic RNA fragments.