N ^τ-methylhistamine concentrations in plasma and urine were determined using a newly developed simultaneous determination for histamine andN ^τ-methylhistamine, based on isotope dilution mass fragmentography. Three groups of patients were investigated: patients receiving intravenously-administered iodamide for excretory urography, patients receiving a wasp-sting challenge, and patients treated with an intravenously-administered muscle relaxant. In all patients showing a distinct systemic anaphylactic or anaphylactoid reaction histamine andN ^τ-methylhistamine concentrations were found to be elevated. From the results of this study it can be concluded thatN ^τ-methylhistamine in plasma and urine is a good parameter for histamine release, and that the determination of this histamine metabolite are less hampered by possible artefacts (due to basophil disrupture, a very short half-life time or bacterial production) than determinations of histamine itself.