Earlier studies have reported the presence of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in the plasma of patients with cystic fibrosis (CF), but the results have been inconsistent. To investigate the relationships among plasma IL-1 alpha, IL-1 beta, TNF, lipopolysaccharide (LPS), and clinical status, measurements were made before and after 14 days of intravenous antibiotic therapy in 13 patients with CF. In addition, whole blood cytokine production rates were measured in 18 hr cultures stimulated with 10 micrograms/mL LPS or sterile saline (control). On admission, patients with CF had significantly greater plasma levels of LPS and IL-1 alpha compared with 20 healthy adult controls. In response to antibiotic therapy, the patients had statistically significant increases in weight, oxygen saturation, chest radiograph score, and forced expiratory volume in 1 second. They had significant decreases in pulse rate, residual volume/total lung capacity ratio, white blood count, neutrophil count, LPS concentration, and resting energy expenditure per kg body weight. There were no significant changes in the plasma concentrations of IL-1 alpha, IL-1 beta, or TNF and no significant changes in the basal or stimulated whole blood production rates of IL-1 alpha, IL-1 beta, or TNF. The immunological variables did not correlate significantly with clinical measurements of severity or the presence of fever. It is likely that in CF local pulmonary effects of cytokines are of more pathophysiologic significance than systemic effects.