Medusahead is an introduced, winter-annual grass covering millions of hectares of the semiarid West. It forms exclusive stands and has a dense thatch cover that resists the establishment of desirable species. Prescribed fire can remove medusahead litter and improve plant establishment. Medusahead control is fundamental to establishing desirable species that will, in turn, resist further invasion. Imazapic is an effective herbicide for control of medusahead, but more information is needed on its effects on desirable species. Our objectives were to test how imazapic application rate and timing affected medusahead, seeded desirable species, and other nontarget vegetation on burned and unburned rangeland in southeast Oregon. We burned existing medusahead infestations at two different sites in June 2003. Following the burn, imazapic was applied at rates of 0, 35, 70, 105, 140, 175, and 210 g ai/ha between July and October of 2003 in a randomized strip-plot design. In November 2003, monocultures of seven desirable species were drill-seeded across the imazapic treated areas. Data on cover and density of medusahead and seeded species were collected in 2004 and 2005. Cover data of nontarget species were collected in the summer of 2005. Medusahead cover was highest in control plots and lowest in plots that received the highest herbicide application rates. Medusahead cover was lower in burned plots. The effect of imazapic on nontarget vegetation was less clear. Seeded species established in the study plots, but their response to herbicide rate showed few consistent patterns; some of the seeded species showed little response to herbicide, whereas others appeared to establish best at different herbicide rates, depending on site and whether the plots were burned or unburned. Site and burn treatment also affected how imazapic rate or application month influenced cover of perennial or annual grasses or forbs.