A rapid and sensitive liquid chromatographic (LC) method for determination of trace amounts of chloramphenicol (CP) in animal tissues has been developed. Chloramphenicol identity is confirmed by gas chromatography-mass spectrometry (GC-MS). CP can be routinely quantitated by LC at 10 ppb with 75% recovery, and GC-MS selected ion monitoring permits complete identification at concentrations as low as 5 ppb. Residues were determined in chicken tissues after intramuscular injection of CP. Depletion was rapid with no residues detected in muscle after 8 h, while 15-30 ppb CP was still determined and identified in the liver.