Tylosin, a macrolide class of veterinary antibiotic compounds, has been widely used in animal production for preventing and treating diseases as well as promoting growth.  This study investigates the environmental factors controlling the behaviors of tylosin in soil and manures.  Tylosin sorption in soil and manure was greatly affected by matrix pH, organic matter, ionic strength, redox potential, and clay type. Increasing pH and ionic strength generally decreased tylosin adsorption by clay minerals. Tylosin was likely intercalated into interlayer spacing of clay minerals upon adsorption. Removing organic matter from original biosolids-impacted soils increased tylosin adsorption dramatically especially at low solution pH. Redox potential had significant effect on tylosin interaction with dairy lagoon sediments. Poultry manures treated with different minerals showed significant effect than the control on the runoff loss of tylosin from soil. These results have significant implications in understanding and managing tylosin runoff in soil environment.