Leafy spurge is an exotic perennial weed that infests more than 1 million ha in North America and reduces rangeland carrying capacity. Experiments were initiated on range sites in Nebraska and North Dakota in 1994 and 1995 to determine the response of leafy spurge and other vegetation to AC 263,222. Herbicide treatments evaluated included AC 263,222 at 0 to 280 g ai/ha, picloram at 560 g ai/ha plus 2,4-D at 1,120 g ae/ha, and quinclorac at 1,120 g ai/ha. In Nebraska, a single application of AC 263,222 in the fall at 140 g/ha provided ≥ 90% leafy spurge control 11 to 12 mo after treatment. At Jamestown, ND, leafy spurge control increased to almost 90% and stem density declined to two shoots/m2 12 mo after the second consecutive fall application of AC 263,222 at 140 g/ha. At Hankinson, ND, leafy spurge control was ≤ 50% when AC 263,222 was applied in the fall only, but increased to > 80% when AC 263,222 was applied in the fall and again at 70 or 140 g/ha in the spring. There were no differences in herbage biomass of established cool- and warm-season grasses where AC 263,222 at 140 g/ha, picloram plus 2,4-D, quinclorac, or no herbicide was applied in the fall. In contrast, application of AC 263,222 in the fall and again in the spring usually reduced cool-season grass biomass.