To understand the role of enterotoxin (Ent) plasmids in epidemics of enterotoxigenic (ET) Escherichia coli diarrhea in the United States, we studied the genetics of Ent plasmids in relation to E. coli serotypes and R plasmids. Twenty-nine ET E. coli strains, including all epidemic isolates available at the Centers for Disease Control, Atlanta, Ga. (CDC), were assessed for the ability to transfer antimicrobial resistances (if present) by conjugation, to mobilize a nonconjugative R plasmid, and to cotransfer enterotoxigenicity with R determinants. Of the 12 ET E. coli strains isolated in the United States, 5 were able to transfer R plasmids; one strain cotransferred detectable enterotoxigenicity. Another four U.S. isolates were able to mobilize plasmid DNA, but no toxin production was detected in transconjugants. Of 17 resistant ET E. coli from South Asia, 13 were able to transfer R plasmids; 5 of those 13 cotransferred detectable Ent plasmids. In all, 22 ET E. coli strains (76%) were able to initiate conjugation and genetic transfers. Six of these strains (20%) were able to cotransfer enterotoxigenicity with a conjugative R plasmid at a detectable frequency. One of the six strains transferred R and Ent determinants on a single plasmid. These data are addressed in relation to the observed immobility of Ent and R during outbreaks of ET E. coli, the efficacy of prophylactic tetracycline, and the worldwide occurrence of a limited number of ET E. coli serotypes.