Barthwell resigned her position in July 2004 for a possible run for the United States Senate from Illinois with the Republican Party. Earlier, nominee Jack Ryan had dropped out of the race, leaving the party without a candidate. Barthwell was favored by moderates on the Illinois Republican Central Committee to run against Democrat Barack Obama, but conservative committee members ultimately won out after two days of gridlock, forcing the committee to select former United NationsAmbassador and perpetual candidate Alan Keyes. Keyes went on to lose to Obama in a landslide.