The measurement of histamine in samples obtained from human lung is important in determining the roles of histamine and mast cells in normal and disease states. We, therefore, compared different assays for the measurement of histamine in human lung samples. Both a single isotope enzymatic assay and a radioimmunoassay (RIA) were capable of accurately measuring the low concentrations of histamine (0.05-2.0 ng/ml) normally found in bronchoalveolar lavage fluid. The RIA was also able to measure histamine levels up to 1500 ng/ml in human lung tissue samples. Moreover, the RIA measurement of high levels of histamine in lung samples compared favorably to an automated spectrofluorometric method. Unlike either the single isotope enzymatic assay or the automated spectrofluorometric assay which have effective capabilities at less than and greater than 2 ng/ml, respectively, the RIA can accurately measure histamine levels from 0.05 to 1500 ng/ml. Since the RIA is easier to perform, less costly, and has a wider range of effectiveness, this assay should prove valuable in assessing histamine levels from a variety of human lung samples, thereby, providing an avenue to elucidate the roles of histamine and mast cells in lung functions.