The spread of wild-type Escherichia coli bearing a transferable plasmid was studied in a farm environment. E. coli of bovine and porcine origin were marked by resistance to nalidixic acid (Nar) or rifampicin (Rfr), and a transferable, multiple resistance plasmid (pSL222-1 derivative of plasmid R222) was introduced by conjugation. In separate experiments, the two mutant derivatives were fed back to the respective host animals, which were housed adjacent to, but separate from, one or more "recipient" animals. No antibiotic was given. Although the Rfr derivatives declined rapidly to undetectable levels within 1 week, the Nar mutants of bovine and porcine origin persisted in the original hosts and in their bedding throughout most of each 4-month test period. Test bacteria were isolated from mice residing in the same pen as the donor animals and from multiple secondary hosts having direct or indirect contact with the inoculated donors, but not from neighboring animals maintained in isolation. The bovine mutant was excreted by two caretakers for greater than 4 weeks and was recovered for 4-6 weeks from pigs, fowl, and flies. Although the porcine mutant appeared to colonize less effectively, it spread rapidly to flies and mice and was recovered transiently from humans and fowl. Despite high transfer rates of plasmid pSL222-1 from E. coli K-12 in vitro, transfer of the plasmid from the animal E. coli host was very low and transfer in vivo was not detected among indigenous gut or environmental bacteria. E. coli of animal origin can spread rapidly and can colonize the intestinal tract of humans and of other animals in the absence of antibiotic selection.