The aim of this, study was to develop a multi-residue method for the analysis of penicillins in animal tissue. Matrix solid phase dispersion (MSPD) was employed to extract the residues and the extracts were then cleaned-up by C-18 solid phase extraction (SPE). Pre-column derivatisation using acetic anhydride and 1,2,4-triazole in the presence of mercuric chloride was employed to allow detection at 325 nm. Gradient elution was required to elute amoxicillin, ampicillin, penicillin G, cloxacillin and dicloxacillin derivatives from a C-18 reversed phase column using phosphate buffer-acetonitrile mobile phase. The developed method had a limit of detection of 20 ng g(-1) and had recoveries in the range 40-90% for the 5 drugs in samples fortified at 40 and 200 ng g(-1); the maximum residue limits (MRLs) for these drugs were in the range of 50-300 ng g(-1) (ppb).