A comparative sequence analysis of part of the RNA genome containing the poly(A) signal of different groups of immunodeficiency viruses, including human types 1 and 2, simian types mandrill, african green monkey, and sykes, reveals the conservation of certain structural features despite the divergence in sequence. In all cases, the AAUAAA signal was found to be flanked by nucleotide segments that can basepair, thus forming a hairpin structure with the poly(A) signal in the single-stranded loop. The fact that both this stem-loop structure and its thermodynamic stability are well conserved suggests a biological function for this structure motif [corrected]. Consistent with this idea, we demonstrate that stabilization or destabilization of the stem region does severely inhibit the replication potential of the HIV-1 virus.