Many cystic fibrosis patients with Pseudomonas lung infections receive intravenous (IV) antibiotics and chest physiotherapy (CPT) at home. Previous studies have suggested that home care, in the setting of a clinical study, is as efficacious as hospital care. This report compares the outcomes of home care with minimal supervision to outcomes of hospital care. We compared two groups of similar age and severity of lung impairment. Patients met strict definitions for home or hospital treatment (27 home care courses/33 hospital care courses). Five patients completed six courses of both home care and hospital treatment. Treatment in both groups included intravenous antibiotics and CPT. Primary outcome measures included changes in pulmonary function between the start of treatment and after 2 weeks of therapy, duration of treatment, and intervals between antibiotic courses. In hospitalized patients, forced vital capacity (FVC) increased by 17.4 +/- 3.1% (mean +/- SEM), and forced expiratory volume in one second (FEV1) increased by 23.3 +/- 4.1%, both significant at P < 0.001. The FVC and FEV1 of patients treated at home increased by 10.2 +/- 2.0% and 13.7 +/- 2.6% respectively, neither of which was a significant improvement. Similar results were found in the five patients completing both home and hospital courses. The average duration of treatment was twice as long and time between IV antibiotic courses only two-thirds as long for those treated at home compared with the hospitalized patients. Previous reports have claimed that home care in the setting of a prospective study is as efficacious as hospital care. Our experience indicates that routine home care with minimal supervision of patients is less effective than hospital care. Furthermore, home care as delivered to patients in this report increased the overall cost of care by as much as 30% because of longer and more frequent courses of antibiotic therapy.