Recurrent sinusitis (RS) is a very common clinical problem for which no underlying cause can generally be ascertained. We examined nasal mucosal responses in 14 patients with RS to determine if a relative deficiency in secretion of glandular antimicrobial factors might play a role. Twenty-four subjects with no history of sinusitis were studied concurrently as normal control (NC) subjects. RS was defined by two or more episodes of acute sinusitis per year for 2 or more years. After provocation with 25 mg of methacholine or 1 mg of histamine, nasal washings were analyzed for total proteins: the plasma protein albumin, IgG, and nonsecretory IgA (nsIgA), and the glandular proteins secretory IgA (sIgA), lactoferrin (LFN), and lysozyme (LZM). Although baseline secretions in patients with RS were relatively enriched with LFN and LZM as compared to that of secretions in NC subjects, patients with RS had a blunted cholinergic response with decreased secretion of albumin, IgG, nsIgA, sIgA, and LZM. Histamine responses were equivalent in both patients with RS and NC subjects. After 4 to 12 months of medical treatment, the abnormal cholinergic responses improved on repeat methacholine challenge in all eight subjects with RS rechallenged. Thus, patients with RS have a reversible reduction in nasal mucosal secretory responses to cholinergic stimulation. Since glandular secretions are rich in antimicrobial factors, such as LFN, LZM, and sIgA, it appears possible that the inability to secrete glandular proteins normally may predispose to recurrent infections.