Macrolides can be clinically effective in chronic rhinosinusitis (CRS). However, little is known about how these drugs affect pathophysiological features of CRS in vivo. In the present study, patients with CRS were subjected to long-term treatment with clarithromycin. Nasal lavages with and without histamine (40 and 400 姠ml-1) were carried out prior to and late into the treatment period. Histamine was included as a tool to produce plasma exudation, a process known to move free cellular products from the mucosal tissue into the airway lumen thereby enriching nasal surface liquids with such products. Interleukin-8 (IL-8), myeloperoxidase (MPO), eosinophil cationic protein (ECP), a2-macroglobulin and fucose were monitored as indices of pro-inflammatory cytokine production, neutrophil and eosinophil granulocyte activities, plasma exudation and mucinous secretion, respectively. Clarithromycin reduced the lavage fluid levels of IL-8 at the low-dose histamine observation (P<0簰1). There was a trend towards reduced MPO by the treatment, whereas ECP was significantly reduced at the low-dose histamine observation (P<0簵). a2-Macroglobulin was reduced by clarithromycin (saline lavages) (P = 0簵), whereas fucose was unaffected. The exudative responsiveness to high-dose histamine was significantly reduced by the treatment (P<0簵). Furthermore, significantly lower levels of fucose were observed at the low-dose histamine observation (P<0簱). We conclude that long-term clarithromycin treatment likely exerts an anti-inflammatory effect in CRS.