Much research has been conducted on mesotrione activity on crops and weeds, but information is lacking in regards to the relative contribution of soil and foliar absorption of mesotrione. Three experiments conducted at Virginia Tech's Glade Road Research Facility in Blacksburg, VA, evaluated the effects of 50 and 90% relative humidity (RH) on the activity of mesotrione applied to foliage, soil, and soil plus foliage. Tall fescue injury ranged from 0 to 21% and was significant in 6 of 20 comparisons. Three of these injury events were caused by soil plus foliar applications, which were always more injurious than foliar only applications, which were more injurious than soil-only applications. Both application placement and RH significantly influenced smooth crabgrass responses to mesotrione. Smooth crabgrass phytotoxicity was lowest when mesotrione was applied only to foliage and highest when mesotrione was applied to soil and foliage. Increasing RH from 50 to 90% caused a 4- to 18-fold increase in plant phytotoxicity when mesotrione was applied only to foliage. By dissecting the plant canopy, it was noted at 14 d after treatment, when averaged over RH, that white leaves comprise 16% of leaves when only foliage was treated and 55 and 62% when applied to soil plus foliage and soil only, respectively. Furthermore, white tissue was found predominately in the two youngest leaves when mesotrione was applied to soil or both soil and foliage, but in older leaves when applied only to foliage. Data indicate mesotrione entering plants through soil travels quickly to growing points and has an equal or greater effect on plant phytotoxicity than foliar-absorbed mesotrione. In addition, foliar-absorbed mesotrione appears to increase in plants significantly with increasing RH, but does not move rapidly to growing points.