Rationale: Transforming factor β1 (TGF-β1) genetic polymorphisms have been identified as a modifier of cystic fibrosis (CF) lung disease severity. However, few data link TGF-β1 protein levels and clinical markers of CF lung disease severity. Objectives: To determine the association between protein levels of TGF-β1 in pediatric CF bronchoalveolar lavage fluid (BALF) and clinical parameters of CF lung disease severity. Methods: Total TGF-β1 was measured in BALF from 30 pediatric CF patients and 12 non-CF disease controls undergoing clinically indicated flexible bronchoscopy, and compared to four indicators of clinical disease: infection, inflammation, pulmonary function, and recent/recurrent hospitalization. Results: TGF-β1 was elevated in CF BALF compared to non-CF controls (135±15 pg/ml vs. 57±10 pg/ml, P<0.01). In CF BALF, increased TGF-β1 was associated with elevated BALF PMN % (r=0.67, P<0.01). BALF TGF-β1 was increased in CF subjects whose FEV1 after the completion of antibiotic therapy remained below CF age-normative median values (205.9±20.5 pg/ml vs. 106.4±24.0, P=0.01). BALF TGF-β1 was increased in CF children hospitalized in the previous year compared to those not recently hospitalized (169.9±21.6 pg/ml vs. 107.5±17.5 pg/ml, P=0.04). Neither the presence of a bacterial pathogen nor bacterial quantity was associated with BALF TGF-β1. Conclusions: In CF, BALF TGF-β1 is elevated compared to non-CF controls. Increased BALF TGF-β1 is associated with neutrophilic inflammation, diminished lung function and recent hospitalization. Further investigation is needed to address mechanisms behind these associations. © 2009 Wiley-Liss, Inc.