Chloromethyldimethylsilyl (CMDMS) ethers are useful derivatives for combined gas chromatography-mass spectrometry. They have characteristically longer retention times than the corresponding trimethylsilyl (TMS) derivatives, and this permits effective fractionation of mono-, di-, and trihydroxy steroids. CMDMS ethers provide mass spectra comparable with those of TMS ethers, but ions containing the CMDMS group are readily recognisable in the former by virtue of the two abundant natural isotopes of chlorine. This facilitates interpretation of spectra and may be expected to aid the location of drug metabolites by selective ion monitoring.