Inducing sputum using hypertonic saline is a noninvasive method to investigate airway inflammation in people with asthma. However, hypertonic saline may also induce bronchoconstriction in some patients. The aim of the study was to examine whether the overall safety of using hypertonic saline to induce sputum in patients with mild to moderate asthma could be extended to patients with severe and/or uncontrolled asthma. Nine control subjects and 64 asthmatic patients with varying severity of the disease (FEV1 40-126% predicted values) were studied. Twenty-one of those patients had uncontrolled asthma. Sputum was induced in a standardized manner using hypertonic saline. The safety of the procedure was evaluated by assessing the clinical response and measuring FEV1 just before and during sputum induction. The procedure was well tolerated in most patients, but it had to be stopped due to side effects in 11.6% of patients with severe asthma. None of the side reactions were severe. Few patients with uncontrolled (17.3%) or severe asthma (18.6%) had a drop in FEV1 of 10-20%. The fall in FEV1 was significantly greater in patients with severe asthma than those with mild disease (p < 0.02 Mann-Whitney U test). We conclude that hypertonic saline-induced sputum is a safe technique even in patients with severe asthma.