Antisense RNAs regulate expression of target genes in a variety of ways--transcription termination, translation initiation, and mRNA stability. We describe a case in which the target gene encodes two polypeptides, and antisense RNA causes a switch in its translation by selectively inhibiting synthesis of one of the polypeptides. Bacteriophage P22 is a temperate Salmonella phage; in the prophage state it expresses only a handful of its genes. One of these genes, sieB, aborts the lytic development of some phages. P22 itself is insensitive to the lethal effect of SieB because it harbors a determinant called esc. We show that the sieB gene encodes two polypeptides--SieB, which is the exclusion protein, and Esc, which is a truncated version of SieB that inhibits its action. Superinfecting P22 synthesizes an antisense RNA, sas, that inhibits synthesis of SieB but allows continued synthesis of Esc, thus allowing P22 to bypass SieB-mediated exclusion. This translational switch induced by sas RNA is essential to vegetatively developing P22; a mutation that prevents this switch causes P22 to commit SieB-mediated suicide. Finally, we show that P22's Esc allows it to circumvent the SieB-mediated exclusion system of bacteriophage lambda.