To test the hypothesis that viral respiratory infections cause symptoms by activating mucosal mast cells to release mediators active on vasculature and mucosal glands, the presence of histamine in nasal secretions was assessed during natural colds and rhinovirus infections. Secretions were collected either with saline washes of the nasal cavity or by forcibly blowing into a beaker, and histamine was assayed spectrofluorometrically. In blown secretions from uninfected subjects, large variations were seen between individuals (ranging from 3 +/- 2 to 59 +/- 32 ng/ml), and equally large variations were seen from day to day in given subjects. Infection with rhinovirus and with influenza A did not change these concentrations significantly. In general, both with blown nasal secretions and with nasal washes, histamine concentrations tended to be lower during infection. Concentration of another preformed mast cell mediator, TAME-esterase, also was not elevated during infection. Thus, these data do not support an hypothesis that mast cell activation occurs during rhinovirus infections.