The chromatographic performance of erythromycin A (EA) is improved significantly over that achieved on polymeric columns by using a sterically shielded octyldiisopropylsilica (Zorbax Rx-C8) column and a neutral mobile phase consisting of 5 mM aqueous sodium perchlorate—acetonitrile (50:50). This mobile phase facilitates electrochemical detection of EA at the 3-pmol level. Temperature control of both column and detection cell is important for minimizing detector noise and drift. A clean-up procedure, based on aminopropylsilica solid-phase extraction, allows the detection of EA in salmon flesh down to the 0.2-ppm level. Some of the metabolites of EA that retain the tertiary amine may also be detected by this method. ; Peer reviewed: Yes ; NRC publication: Yes