During 24 months in an uncontrolled, retrospective study of 268 patients with cat-scratch disease (CSD), 202 were treated with 18 different antimicrobial agents. Criteria for antibiotic effectiveness were established. One or two antibiotics were taken separately for at least 3 to 5 days by 202 patients with CSD. Outcome was determined by follow-up examinations and telephone. Effectiveness of antibiotic therapy was based upon 3 or more days of therapy and clinical improvement of the patient with absence of and/or a decrease in malaise, fatigue, fever, headache, anorexia, lymphadenopathy and, in 90 patients, a declining or normal sedimentation rate. Of 18 different antimicrobials prescribed, 14 commonly used antibiotics were judged to be of little or no value in treatment of CSD. Four antimicrobials were efficacious. Efficacy of the three oral drugs in decreasing order was: rifampin 87%, ciprofloxacin 84%, trimethoprim-sulfamethoxazole 58%. Gentamicin sulfate intramuscular was 73% effective. Antibiotic therapy can be considered for patients with severe cat scratch disease. Conservative, symptomatic treatment is recommended for the majority of patients with mild or moderate CSD.