Escherichia coli has been associated with a colonization factor antigen responsible for the bacterial adherence to the intestinal mucosa. This colonization factor is also responsible for haemagglutination. Among 32 antibiotics tested, only tetracyclines, chloramphenicol and nafcillin inhibit haemagglutination. Tetracycline hydrochloride, tetracycline phosphate and doxycycline are the most effective, followed by oxytetracycline, minocycline, chloramphenicol and nafcillin. Doxycline at a concentration at 0.8 mg/ml in buffered saline, chloramphenicol at 12.8 mg and nafcillin at 31 mg inhibit haemagglutination in 2 h. The inhibition of haemagglutination occurs both with E. coli susceptible and resistant to doxycycline. Pretreatment of crythrocytes with doxycycline does not prevent inhibition of haemagglutination where as pretreatment of E. coli does, suggesting that doxycycline acted on the bacteria. Once haemagglutination had occurred, doxycycline can reverse the haemagglutination, "unhooking" the bacteria from the erythrocytes. These data raise the possibility that some antibiotics may prevent adherence of E. coli to the intestinal mucosa, regardless of the susceptibility or resistance of the bacteria by a direct effect on the colonization factor antigen. Furthermore, some antibiotics may be able to detach the bacteria once adherence to the mucosa has occurred.