Bronchial responsiveness to methacholine or histamine increases at night and may contribute to the mechanisms of nocturnal asthma. Hypertonic saline (HS) is a more clinically relevant stimulus for the diagnosis and assessment of the severity of asthma, but the circadian variation in bronchial responsiveness to hypertonic challenges has not been addressed. The aim of this study was to compare the responsiveness to hypertonic saline at 4:00 AM and at 4:00 PM. Eighteen diurnally active patients (11 women) with asthma, 31 +/- 9 years of age (mean +/- SD) and with a forced expiratory volume in 1 s (FEV(1)) of 79.11% +/- 12.85%, underwent two challenge tests (4:00 AM and 4:00 PM) in random sequence separated by an interval of 7 days. The challenge test consisted of inhalations of 4.5% saline with increasing doses by doubling the duration of nebulization (0.5, 1, 2, 4, and 8 min). The inhalation continued until a drop of 20% in FEV(1) was achieved or total time of 15.5 min. The provocative dose that caused the 20% drop in FEV(1) (PD(20)) was calculated. Differences were found between 4:00 PM and 4:00 AM values for inhalation times [3.80 +/- 3.57 min and 2.19 +/- 2.42 min (p = 0.001), respectively] and for PD(20) [4.94 +/- 6.77 ml and 2.93 +/- 4.74 ml (p = 0.002), respectively]. Eight patients with a home-assessed nocturnal peak expiratory flow (PEF) drop of more than 15% formed the nocturnal asthma group. The behavior of these patients was similar to that of the non-nocturnal asthma group. We conclude that the bronchial responsiveness to HS increases at night.