The increased bronchial production of leukotriene C4 (LTC4) in asthma is assumed to derive from infiltrating eosinophils expressing LTC4-synthase (LTC4S). Multicolor immunohistofluorescence examination of bronchial cryosections from 30 treated, untreated, or bronchial antigen-provoked aspirin-tolerant individuals with asthma and nine control subjects revealed that the dominating LTC4S-expressing cells were mast cells (> 80%), and not eosinophils. Whereas 95% of the mast cells expressed high levels of LTC4S, only 8-27% of the eosinophils expressed low levels. Image analysis revealed a significantly higher LTC4S expression levels in mast cells than in eosinophils. The bronchial mRNA levels for LTC4S did not correlate with the densities of LTC4S-positive eosinophils or mast cells. Treated individuals with asthma with more than 12% reversibility had significantly higher density of LTC4S-positive mast cells than those with less reversibility, and it correlated significantly with reduction in lung function (FEV1-predicted), both before and after salbutamol inhalation. Thus, mucosal mast cells, and not eosinophils, were the dominating LTC4S-containing cells in both untreated and treated aspirin-tolerant asthma. The density of LTC4S-positive mast cells correlated, moreover, with both the reduction in lung function and the degree of reversibility in treated asthma.