Low body weight and loss of bone mass are major problems in adults with cystic fibrosis (CF) and chronic pulmonary infection. Although these complications probably have a multifactorial origin, we hypothesized that the continuous acute-phase inflammatory and catabolic state may contribute. We determined body composition, bone turnover, physical activity, and circulating interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and their soluble receptors in 22 adults with CF and 22 age- and sex-matched healthy subjects. Comparisons were also made within patients before and after treatment of an exacerbation of respiratory symptoms. The patients had a lower mean (95% confidence interval [CI]) fat-free mass (FFM) 39.9 (36.3, 43.6) kg than healthy subjects, 49.4 (45.1, 53.7) kg, p < 0.05. The patients were in negative nitrogen balance and 20 had bone mineral density (BMD) Z scores </= 2.5 SD (n = 13) or </= 1 SD (n = 7) at least at one site. They had increased bone collagen breakdown, greatest in those with a reduced FFM. BMD was related to FEV(1) (r = 0.44), IL-6 (r = -0.60), and TNF-alpha-soluble receptors (r = -0.42, r = -0.50). Patients with a low FFM had greater concentrations of IL-6, which suppressed less after antibiotic treatment than in those with a normal FFM. Those with a low FFM were more catabolic and less active than those with a normal FFM. The association between altered body composition, catabolic status, and circulating inflammatory mediators suggests that chronic pulmonary infection in adults with CF may be a contributory factor in the long-term complications of low weight and bone disease.