The following alkylation methods for the determination of indometacin in plasma by electron capture gas chromatography are compared: 1, alkylation with diazopropane; 2, extractive alkylation; 3, alkylation by a solid-liquid phase transfer catalysed process. The drug in plasma at pH 4.0 is initially extracted with heptane containing 5% n-pentanol. The methyl ester of indometacin is based as internal standard. After alkylation to the propyl ester according to one of the three alkylation methods, indometacin can be determined down to 5 ng per sample by electron capture gas chromatography. The relative standard deviations (n = 10) at the 200 ng level are 5.1% for the alkylation with diazopropane, 7.5% for the extractive alkylation technique and 3.5% for the alkylation by the solid-liquid phase transfer catalysed process. The comparatively low value obtained by the last method indicates that decomposition of indometacin can be avoided under such mild conditions.