Evaluation of antibiotic efficacy for infections in previously well individuals is based on eradication of the bacterium and resolution of the signs and symptoms of inflammation. In patients with cystic fibrosis, these criteria are less applicable: systemic signs of inflammation (fever, leukocytosis, and increased erythrocyte sedimentation rate) are variably present, and bacteria are present in the lower respiratory tract after clinical improvement. Administration of a variety of antibiotics produces resolution of subjective signs and symptoms and improvement in pulmonary function tests. Because of the cost of therapy, the need to evaluate new and potentially toxic antibiotics, and the desire to provide optimum care, the evaluation of therapy needs to be objective. Controlled studies evaluating efficacy in a blinded fashion and assessing lung function and resolution of local pulmonary inflammation may provide reliable data on antibiotic effectiveness in CF.