One class of mutations in the envZ gene of Escherichia coli K-12 confers a pleiotropic defect on the expression of several genes, including ompF, lamB, and phoA, that are otherwise not commonly regulated. Four second-site mutations that suppress this transcriptional defect have been isolated by using a procedure that circumvented the problem of intragenic suppressors, including true revertants. All four mutations have been mapped to the genes of the alpha operon and have been assigned tentatively to the gene rpoA, which specifies the alpha subunit of RNA polymerase. The mutations, referred to as sez (for suppressor of envZ), did not appear to confer a phenotype on an otherwise wild-type strain and did not suppress the transcriptional defects conferred by several other phenotypic classes of envZ mutations, including amber mutations. Our results led us to postulate that the alpha subunit or some other component of the alpha operon plays a role in determining the specificity of gene expression.