Field and greenhouse studies were conducted near Painter, VA, in 1999, 2000, and 2001 to evaluate mesotrione postemergence for control of horsenettle in corn. Mesotrione at 105 g ai/ha controlled horsenettle at least 80% in all studies, and in 2001, after two consecutive annual applications, mesotrione controlled horsenettle up to 91%. Additions of primisulfuron, dicamba, and 2,4-D to mesotrione did not increase horsenettle control. Occasionally, combinations of dicamba with mesotrione controlled horsenettle less than did mesotrione alone, and primisulfuron combinations with mesotrione delayed or reduced development of bleaching symptoms associated with mesotrione. Initial horsenettle response to mesotrione was increased by addition of 280 g ai/ha atrazine; however, late-season horsenettle control was not improved by atrazine. Two consecutive annual applications of mesotrione alone decreased horsenettle biomass > 89%. Treatments of primisulfuron plus dicamba, primisulfuron plus CGA 152005 plus dicamba, and 2,4-D plus dicamba provided similar horsenettle control and biomass reductions as did 105 g/ha mesotrione alone.