In this paper a new method for the determination of 2,4,6-trichloroanisole (TCA) and 2,4,6-tribromoanisole (TBA) in wine samples is presented. Headspace single-drop microextraction (HS-SDME) was used for the extraction and preconcentration of the analytes, followed by analysis by gas chromatography and electron-capture detection (GC-ECD). The variables affecting extraction efficiency were optimized using fractional factorial experimental and Box-Behnken designs. The external calibration procedure was successfully carried out using a synthetic wine solution and diluted red wine samples. The method was also applied to white wine samples. Excellent detection limits of 8.1 and 6.1 ng L(-1) were achieved for TCA and TBA, respectively. Good precision and accuracy were obtained.