The effect of host determinants on expression of plasmid-coded heat-labile enterotoxin (LT) was examined. A collection of LT plasmids was introduced into isogenic strains of Escherichia coli K-12 strains containing the wild type or hypertoxinogenic (htx-2) allele. For each plasmid tested, production of LT increased by approximately 1.5- to 3-fold in the host containing htx-2, indicating that the htx-2 allele affects a regulatory function for LT production that is common to many different enterotoxin plasmids. LT plasmids from E. coli were also introduced into strains of Shigella flexneri, Shigella sonnei, Citrobacter freundii, Enterobacter cloacae, Klebsiella pneumoniae, and Salmonella typhimurium. The plasmids were stably maintained and determined production of LT in those genera, although the amounts of LT produced varied by more than 50-fold. These observations demonstrate that host factors have an important role in determining the level of expression of plasmid-coded LT genes and support the hypothesis that interspecific, conjugal transfer of enterotoxin plasmids may confer enterotoxigenicity to a wide variety of potentially pathogenic enteric bacteria.