SummaryStudies using the guinea pig ileum bioassay technique have previously shown that patients with either asthma or chronic bronchitis have increased amounts of histamine in their sputum. Because of the limitations of this assay technique, a spectrofluorometric method for measuring the histamine content of sputum was developed. Using this technique it was found that the mean histamine concentration of sputum from patients with bronchogenic carcinoma or pneumonia was not significantly different from the mean value for sputum collected during a remission phase from patients with either chronic bronchitis or asthma. However, the mean values in patients with asthma or chronic bronchitis during an exacerbation were significantly higher and returned to basal values as the airways obstruction improved. There was no significant difference in sputum histamine concentration between those patients with extrinsic atopic asthma and those with late onset cryptogenic asthma during an exacerbation although the value in patients with an exacerbation of chronic bronchitis was significantly less.These results indicate that mediators of immediate hypersensitivity may be implicated in the pathogenesis of airways obstruction in disorders other than extrinsic atopic asthma and suggest that histamine release may occur in non‐atopic subjects in response to non‐antigenic stim