The runoff potential of tylosin and chlortetracycline from soils treated with manure from swine fed rations containing the highest labeled rate of each chemical was assessed on several different soil types at different landscape positions.  Slurry manure contained either CTC at 108 μg/g or tylosin at 0.3 μg/g and were applied as surface applications to clay loam, silty clay loam, and silt loam soils at a rate of 0.22 Mg manure/ha. Four sites with different soil types in the eastern South Dakota landscape were used to assess antimicrobial chemical runoff.  Tylosin also was applied directly to the soil surface to examine runoff potential if manure was not present.  A sprinkler infiltrometer was used to apply water 24-hr after manure application with runoff collected incrementally for about 45 min.  Infiltration was 30% higher at the summit than toeslope position when no manure was present.  However, a biofilm crust formed on all manure-treated surfaces and infiltration was impeded with >70% of the applied water collected as runoff.  The total amount of CTC collected ranged from 0.9 to 3.5% of the amount applied whereas tylosin ranged from 8.4 to 12%.  These data indicate that if surface applied manure contains antimicrobials, runoff could lead to offsite contamination.  Shallow or deep injection of manures could be used to limit runoff of manure contaminanats.