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Bartonella henselae infection was established in eight cats of various ages by experimental inoculation. All cats remained persistently bacteremic until they were treated 4 to 7 weeks after primary inoculation. Antibody titers increased and peaked between 4 and 12 weeks for all cats. Treatment with doxycycline for 1 week was effective in suppressing bacteremia in all cats but was effective in clearing infection from only four cats. Amoxicillin, given subsequently, was effective in clearing the infection from three of the remaining cats. One kitten that remained bacteremic was treated unsuccessfully with enrofloxacin, and its bacteremia was finally cleared when it was treated with a clavulanate-amoxicillin combination. After the bacteremia was cleared, with a corresponding reduction in serum antibody titers, all eight cats were rechallenged with B. henselae. None of the cats became bacteremic after secondary challenge, and all had higher and more rapid increases in serum antibody titers than after primary inoculation. The cats became resistant to reinfection following recovery from infection, indicating that immunoprophylaxis in cats might be beneficial in helping to reduce their public health risk.