Domestic cats are the reservoir of Bartonella henselae, the main causative agent of cat scratch disease. We compared B. henselae type I infection characteristics in 6 SPF cats infected with a feline strain (4.8 x 10(7) colony-forming units (CFU)/mL) and in 6 SPF cats infected with the reference Houston I strain (6.6 x 10(6) CFU/mL to 9.6 x 10(7) /mL). All the cats inoculated with the feline strain, but none of the cats inoculated with B. henselae Houston I, developed a fever within 2-12 days (mean: 5.8 days) post inoculation (PI), which lasted for 1-2 weeks. However, all 12 cats became bacteremic. The duration of bacteremia was significantly longer in the cats inoculated with the feline strain (mean: 237 days) than in the cats inoculated with Houston I strain (mean: 60 days) (p < 0.01). Five (83%) cats inoculated with the feline strain and none of the six cats inoculated with B. henselae Houston I had relapsing bacteremia (p = 0.02). IgG antibodies were detected by IFA within 1-2 weeks for both strains, but peaked later (week 10 versus week 3 PI) for the feline strain. By ELISA, using antigens of each B. henselae strain, all 12 cats developed Bartonella specific IgM and IgG antibodies, but the cats infected with B. henselae Houston I antigen yielded significantly lower optical density values (p < 0.05). By SDS-PAGE, PFGE and Western blotting, protein profile differences (84 to 89% homology) were observed between the two strains. If a feline vaccine is to be developed in order to prevent human infection, the choice of the vaccine strain will be critical, since major differences were identified even between strains belonging to the same sero/genotype.