The sieA exclusion system of phage P22, which blocks superinfection by several Salmonella phages, has been shown to prevent expression of all superinfecting phage functions tested. The exclusion mechanism is specific for DNA injected from phage particles, since growth of heteroimmune phage by thermal or zygotic induction is unaffected by the presence of a P22 sieA + prophage. Though superinfecting phage adsorb to P22 sieA + lysogens, injection of superinfecting DNA is apparently incomplete, since the DNA does not become available to a host DNA restriction system. Though it is not extensively solubilized, much of the sieA-excluded DNA is nicked, indicating that at least some of it is ejected from the phage head. The hypothesis that the A exclusion system blocks entry of superinfecting phage DNA explains the observation (Ebel-Tsipis and Botstein, 1971) that the A system also excludes P22 generalized transducing particles. On the P22 genetic map, the sieA gene is located immediately to the left of the mnt repressor gene and to the right of a cluster of genes coding for proteins involved in injection of phage DNA. Since both the sieA and mnt genes are expressed by the repressed prophage, it is possible that they are coordinately controlled.