An assay has been developed for N tau-methylhistamine, a major metabolite of the autocoid histamine, based on gas chromatography-electron-capture negative-ion chemical ionisation mass spectrometry. N tau-Methylhistamine was extracted from urine by cation-exchange chromatography and converted to its di-(3,5-bistrifluoromethylbenzoyl) derivative. The latter has good chromatographic properties and gives a negative-ion mass spectrum with the molecular ion (M., m/z 605) as base peak. A commercially available trideuterated analogue of N tau-methylhistamine was used as internal standard. Basal urinary excretion of N tau-methylhistamine in five normal subjects was found to be 0.21 +/- 0.05 mumol/h (289 +/- 74 mumol/mol of creatinine). This value was not significantly altered in these subjects following the infusion of a subpharmacological dose of histamine. In eight atopic volunteers, basal urinary excretion of N tau-methylhistamine was also not significantly changed following challenge with inhaled allergen.