The objectives of this study were to assess sorption and desorption of tylosin, a macrolide antimicrobial chemical used in swine, cattle, and poultry production, in three silty clay loam soils of South Dakota and compare soil sorption to sand and manure sorption The silty clay loam soils, from a toposequence in eastern South Dakota, standardized sand samples, and swine manure were used in 24-h batch sorption studies with tylosin, concentrations ranging from 25 to 232 mu mole/L. Desorption from soil was conducted over a four-day period. Partition coefficients, based on the Freundlich isotherm (K-f) or K-d values, were calculated. K-f values for the silty clay loams were similar, not influenced by landscape position, and averaged 1350 with isotherm slopes ranging from 0.85 to 0.93. K-f values for sand were dependent on solution/sand ratios and pH, ranging from 1.4 to 25.1. K-d values of manure were dependent on the solution type and ranged from 840 L/kg with urine to about 175 L/kg when sorbed from water. Desorption of tylosin from each soil over the four-day period was < 0.2% of the amount added. The soils' high K-f values and low desorption amounts suggest that once tylosin is in these soils, leaching to lower depths may not occur. However, this does not preclude runoff with soil eroded particles. If tylosin reaches a sand aquifer, through bypass flow or other mechanism(s), movement in the aquifer most likely would occur.