Recent evidence supports a causal relationship between Bartonella (Rochalimaea) henselae, cat-scratch disease (CSD), and bacillary angiomatosis. Cats appear to be the primary reservoir. Blood from 19 cats owned by 14 patients diagnosed with CSD was cultured. Blood samples from cats owned by veterinary students (n = 25) having no association with CSD or bacillary angiomatosis were cultured as controls. Eighty-nine percent (17 of 19) of cats associated with CSD patients and 28% (7 of 25) of controls were bacteremic with Bartonella species (chi-square = 16.47; P < 0.001). Twenty-three isolates were characterized as B. henselae, while one isolate from the cat of a CSD patient appeared to be a new Bartonella species. Thirteen cats remained culture positive during the ensuing 12-month period. Our results support the conclusion that B. henselae is the predominant species involved in CSD and is transmitted by cats. The incidence of Bartonella bacteremia in control cats suggests that B. henselae bacteremia is prevalent among the domestic cat population in the United States.