Aggravation of symptoms in inflammatory airway diseases is common in the early morning hours, but little is known about day-night differences in the occurrence of plasma exudate on the airway surface. We have therefore examined the plasma macromolecules on the nasal mucosa at different time points. The study comprised 20 subjects who had been inoculated (day 0) with coronavirus intranasally. Ten subjects remained healthy and 10 developed common cold with significant symptoms from day 2 to day 6. Starting on day 3 at 8.00 h and repeated at 4 h intervals until 4.00 h on day 4, nasal lavages were carried out by employment of a nasal pool-device which fills the entire unilateral nasal cavity and gently but effectively irrigates its surface. Lavage fluid levels of albumin (Mw 69,000 D) and fibrinogen (Mw 340,000 D) were determined. In the healthy subjects the levels of albumin and fibrinogen remained low throughout the experiment, however, with mean peak values of the two proteins occurring at 4.00 h (p < 0.05 compared to daytime nadir at 16.00 h). In subjects with common cold both albumin (p < 0.05) and fibrinogen (p < 0.01) exhibited marked variation with individual and mean peak levels recorded at 8.00 h day 3, and 4.00 h day 4. These mean peak values were 5-20 times higher (p < 0.01 - p < 0.05) than the mean levels recorded in these subjects at the other time periods. The present data indicate a marked day-night difference in the occurrence of plasma proteins on the airway surface in common cold, whereas in health the difference is much less. We conclude that different-sized plasma proteins may accumulate on the mucosa in healthy airways during late night hours and that in common cold this nocturnal accumulation may be considerably increased.