Nasal challenge of susceptible persons with cold, dry air (CDA) (breathing air at a temperature of -7 to -10 degrees C and a relative humidity of 0 to 10% at a flow rate of 12.5 ml/min for 15 min) stimulates nasal symptoms and release of histamine and other mediators associated with mast-cell activation. To investigate whether such a nonantigenic stimulus induces a late-phase reaction (LPR) in the nose, we challenged 12 preselected volunteers who had previously shown an immediate response to CDA. We monitored the subjects' responses for 10 h by means of symptom diaries and the levels of histamine and TAME-esterase activity in nasal lavage fluids. All 12 subjects showed an immediate response, whereas 8 had a LPR, as indicated by a recurrence of symptoms (rhinorrhea and congestion) hours later, accompanied by an increase in the levels of histamine and TAME-esterase activity. Rhinorrhea and congestion were concomitant with the late reelevation of mediators. Control challenges of these subjects with warm, moist air (WMA), as well as serial nasal lavages without any stimulation of the nose, failed to induce an early- or a late-phase response. The amount of both mediators and symptoms generated during the 10 h after the initial reaction to CDA challenge was significantly greater (p less than 0.02) than after WMA challenge or after performance of nasal lavages without a challenge. The ability of CDA to induce a LPR strengthens the connection between initial mast-cell activation and the occurrence of a LPR.