This retrospective study was designed to evaluate the safety and efficacy of a bronchoprotective sputum induction protocol in moderate to severe chronic obstructive pulmonary disease (COPD). Forty-two adults with COPD (FEV1 = 51.7 +/- 3.2% predicted (mean +/- SEM)) under went sputum induction using a protocol designed to minimize hypertonic saline-induced bronchoconstriction. Hypertonic (3%) saline was used for subjects with FEV1 > or = 50%, and normal (0.9%) saline was used for subjects with FEV1 < 50%. Primary outcomes were change in peak flow, FEV1 and oxygen saturation. Mean decline in peak flow during sputum induction was 13.2 +/- 2.1%. FEV1 fell by 11.4 +/- 2.3%, an absolute fall of 0.14 +/- 0.031. Oxygen saturation did not change. A fall in peak flow of > or = 20% reliably predicted a fall in FEV1 of > or = 20%. Thirty-five of 42 subjects (83.3%) produced an acceptable sputum sample. Sputum eosinophil and neutrophil percentages were 2.8 +/- 0.9 and 73.0 +/- 3.0%, respectively, and were not correlated with changes in peak flow, FEV1 or oxygen saturation. A protocol for sputum induction which restricts the use of hypertonic saline based on lung function is both safe and effective in subjects with moderate to severe COPD.