The glass fiber-based automated chlorometric microtiter plate whole blood leukocyte histamine release test (LHRT) may provide an in vitro correlate to in vivo allergic responses. Depending upon the high affinity of histamine for glass fibers, the fluorometric assay for histamine has a high correlation with radioimmunoassay for native histamine. For the diagnosis of respiratory allergy, up to 90% concordance between basophil histamine release results and skin test results to common inhalant allergens has been noted, although up to 96% concordance of basophil histamine release results in bronchoprovocation tests may occur. In general, the concordance between LHRT results and either skin test results or allergen inhalation challenge results is greater than the concordance between the LHRT results and radioallergosorbent (RAST) results. The LHRT may be a valuable tool for the investigation of drug allergy and food sensitivity. The ability of the LHRT to detect both IgE-mediated and non-IgE-mediated basophil responses is a potential advantage over RAST testing in situations in which the presence of specific IgE directed toward a potential allergen has not as of yet been demonstrated. False-negative LHRT results may occur in 10 to 20% of subjects who have basophils that fail to respond to anti-IgE as a positive control. Advances in both sample and blood and constitution of sample media may minimize this percentage of nonresponding basophils. Differences between mast cell and basophil responses may occur due to functional heterogeneity between basophils and mast cell subtypes.