A rapid and sensitive high performance liquid chromatographic method for the determination of trace amounts of chloramphenicol (CP) in milk has been developed. The antibiotic can be quantitated at a 10 ppb level with a limit of detectability estimated at 5 ppb. Recoveries ranged from 72 to 99.5%. Milking studies have been carried out on goats that received CP either by intramuscular injection or by intramammary administration. CP was measured in milk samples collected 1, 2, 3, 4, 5, 6, 7, 8, 24, 32 h after treatments. No residue could be detected 32 h after treatment. No interfering peaks appeared on control milk chromatograms.