The advent of new methods to detect animal drug residues has resulted in a need to independently validate them. The effects of processing milk on the performance of these methods was evaluated. Antibiotic-free milk samples were spiked with sulfamethazine, penicillin G, and chlortetracycline at levels of 10, 10 and 30 ppb, respectively. Spiked milk and negative control milk was heat-treated, homogenized or heat-treated and homogenized. The procedures evaluated for penicillin detection were Bacillus stearothermophilus disk assay, a HPLC described by Barker et al., Charm II microbial receptor assay, and CITE Probe and LacTek enzyme immunoassays. The procedures evaluated for sulfonamide detection were an HPLC method described by Long et al., Charm II microbial receptor assay, CITE Probe, LacTek and Signal enzyme immunoassays. The methods evaluated for tetracycline detection were a HPLC method described by Long et al., Charm II microbial receptor assay, and LacTek and CITE Probe enzyme immunoassays. The results indicate that the commercial tests and the disk assay were not adversely affected by processing treatments. Significant treatment differences were found when testing raw Charm II data by analysis of variance but these differences did not effect the overall results of the test. Results of the HPLC method were inconclusive for the three drugs tested. / Master of Science