Hydroxymethanesulfonate (HMSA), the bisulfite (HSO3-) adduct of formaldehyde (CH2O), is a common constituent of California acid fogs. HMSA, most stable in a fog pH range of 3 to 5, dissociates at 6.6, the pH of the fluid lining human airways. The dissociation of inhaled HMSA should theoretically generate sulfur dioxide and CH2O, both of which have bronchoconstrictor potential. Thus, we hypothesized that HMSA may have a specific bronchoconstrictor effect independent of its strength as an acid. To determine whether HMSA has such an effect, 19 subjects with mild to moderate asthma were studied using two different protocols. Initially, a mouthpiece study was performed in which 9 subjects, on 2 separate days, inhaled five aerosols containing either sequentially increasing concentrations (0, 30, 100, 300, and 1000 microM) of HMSA in 50 microM sulfuric acid (H2SO4) or 50 microM H2SO4 alone. The subjects inhaled each aerosol for 3 min during tidal breathing at rest. Specific airway resistance (SRaw) was measured before and after each 3-min exposure. There were no significant differences in the mean changes in SRaw among the various aerosol exposures. To confirm this lack of bronchoconstrictor effect of HMSA, we then performed a chamber study in which 10 freely breathing, intermittently exercising subjects were exposed to fog containing either 1 mM HMSA in 5 mM H2SO4 or 5 mM H2SO4 alone for 1 h. SRaw was measured before, during, and at the end of the 1-h exposure.(ABSTRACT TRUNCATED AT 250 WORDS)