Alterations in non-adrenergic, non-cholinergic (NANC) function may contribute to nocturnal asthma. We have attempted to clarify the importance of the NANC system in the circadian variation in airway calibre in mild asthmatics and nocturnal asthmatics. NANC function in the human airway was studied at 0400 and 1600 hours in 12 nocturnal asthmatics and 12 mild asthmatics by measuring oscillatory resistance (Ros) following capsaicin inhalation. Measurements were made after combined beta- and atropinic blockade in the mild asthmatics but after atropinic blockade alone in the nocturnal asthmatics, in whom beta-blockade is contraindicated. To determine whether beta-blockade influences NANC bronchodilatation, we also studied 12 normal subjects with and without beta-blockade at 1600 hours only. The mild asthmatics showed differing (P = 0.007) resistance changes 1-3 min after capsaicin at 1600 hours (fall in Ros + 1%, CI -2% to 3%) from that at 0400 hours (-4%, CI -8% to -1%) but the nocturnal asthmatics showed no significant difference in response to capsaicin at the two times (fall in Ros: 1600 hours -9%, CI -15% to -3%; 0400 hours -3%, -7% to 1%). The normal subjects showed greater (P = 0.0001) bronchodilatation 1-3 min after capsaicin following atropine plus propranolol (-7%, -11% to -3%) than after atropine alone (-2%, -6% to 2%), supporting interaction between the beta-sympathetic and NANC systems in the human airway, NANC bronchodilatation being inhibited by beta-sympathetic activity. Our observations confirm circadian variation in NANC function in mild asthmatics and suggest interaction between the beta-adrenergic and the NANC bronchodilating system in the normal human airway.