Seventy percent of “off the shelf” and tanker milk tested in the northeast U.S. was contaminated with sulfonamide at above 5 ppb with 35% having more than 25 ppb (equivalent sulfamethazine). In this study milk was screened with an A.O.A.C. receptor assay and with a newly developed growth inhibition assay for sulfonamides with sensitivity of 10 - 20 ppb. Sulfamethazine was found as the major sulfonamide contaminant but not the only one as determined by high pressure liquid chromatography and mass spectrometry. An incurred residue study with long acting sulfamethazine boluses showed residue persisting in milk above 25 ppb after 7 d. Sulfonamides are readily available as “over the counter” drugs in agricultural stores and are frequently used for treatment by veterinarians. The regulatory disc assay which is insensitive to sulfonamides failed to protect the milk supply in the Northeast against sulfonamide contamination.