Liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization has been successfully applied to the determination of trans-resveratrol (3,5,4'-trihydroxystilbene) in wine. Of a range of analytical conditions that were tested, optimum results were obtained by the use of reversed-phase high performance liquid chromatography (HPLC) using a mixture of methanol and ammonium acetate as the mobile phase. The negative-ion spectrum of trans-resveratrol showed pseudo-molecular ion, [M ร H] ร , which was the most abundant ion, and low fragment ions corresponding to the losses of hydroxyl groups of the phenol nucleus. Enhanced selectivity for the separation between trans-resveratrol and endogenous wine constituents was afforded by sample purification with a tandem solid-phase extraction method. The approach permits detection at low concentration of trans-resveratrol. The combination of improved sample pretreatment and an isocratic chromatographic system in conjunction with internal standardization forms the basis of a new assay for the quantitation of trans-resveratrol in wine. Full-scan mass spectra were readily obtained from 8 ng of trans-resveratrol, while a limit of detection of 200 pg (signal-to-noise ratio 3) was attained in the selected ion monitoring mode. The application of LC/MS to the determination of transresveratrol in wines is demonstrated by the analysis of red wines.