Imidazoleacetic acid (IAA), a histamine and histidine metabolite, was quantified in human urine by gas chromatography-mass spectrometry (GC-MS). The acid was separated by ion-exchange chromatography, derivatized as the n-butyl ester with boron trifluoride-butanol and the derivative extracted with chloroform. GC-MS analysis was carried out by selected-ion monitoring of ions m/z 81 and m/z 83 corresponding, respectively, to IAA and [15N,15N']IAA used as internal standard. The mean IAA content in urine was about 8.02 nmol/mg of creatinine. The specificity of measurement was rigorously established by GC retention time, peak shape, ion abundance ratios, and recovery experiments. The method is capable of quantifying IAA in 0.05 ml of urine and in amounts as low as 0.20 nmol.