The structural proteins and enzymes of the human immunodeficiency virus type 1 core are translated as part of two polyprotein precursors, Gag and Gag-Pol, which are cleaved by a virally encoded protease. Viruses grown in the presence of inhibitors of the protease contain core particles that are aberrantly assembled, and upon infection of susceptible cells, they do not synthesize viral DNA. Through the use of a proteinase inhibitor (A77003), we determined that the viral reverse transcriptase can efficiently synthesize viral DNA as part of the unprocessed Gag-Pol precursor. We also found that the stabilities of core particles composed of unprocessed precursors were considerably enhanced. These observations suggest that for viruses composed of unprocessed precursors, replication is interrupted before the reverse transcription step.