OBJECTIVE Mucociliary clearance is an important host defense function of the upper respiratory tract that requires the coordinated beating of cilia and results in the transport of mucus to the oropharynx. Guaifenesin is a commonly prescribed drug that is reported to improve the clearance of respiratory secretions. We hypothesized that guaifenesin increases nasal mucociliary clearance related to increases in ciliary beat frequency (CBF) and that a direct relationship exists between nasal CBF and nasal mucociliary clearance. METHODS Double-blind placebo-controlled crossover study. METHODS Ten healthy volunteers with a previous history of sinus disease. METHODS Subjects received guaifenesin or placebo on days 1 to 7 or days 14 to 21. RESULTS In vivo saccharine transit time (STT) was measured by noting the time in minutes required for the subject to taste a saccharin particle placed on the inferior turbinate of the naris. The CBF was determined by video microscopy on ten separate groups of beating ciliated nasal mucosal cells obtained by brushing immediately after each STT determination. We found that there was no significant change between the guaifenesin-or placebo-treated groups from baseline values of STT (p = 0.94) or CBF (p = 0.46). Regression analysis demonstrated no relationship between STT and CBF for repeated measures within subjects (mean r2 = 0.18; mean p = 0.66) and between STT and CBF when all paired measurements were combined across subjects (r2 = 0.47; p = 0.46). CONCLUSIONS We conclude that guaifenesin exerts no measurable effect on in vivo nasal mucociliary clearance or ex vivo nasal ciliary motility in healthy volunteers with previous sinus disease. In addition, there appears to be no relationship between nasal STT measured in vivo and CBF measured ex vivo. The lack of correlation is most likely due to variations in CBF related to sampling artifacts introduced by the nasal brushing process.