The United States has a long history of annexing more and more land. Have there been any occasions where the United States lost land, via war, negotiation/international agreement/international pressure, or other reasons?
In 1963 the US swapped land with Mexico and lost a net 173 acres do to the Rio Grande moving and the border being restored. http://en.m.wikipedia.org/wiki/Chamizal_dispute
A few Territories, which count to my mind (this list is probably what you're looking for).
As for significant handovers:
First, the Philippine Islands are a former U.S. Territory, acquired in the wake of the Spanish-American War. They attained independence in 1946.
Second, the Panama Canal Zone was a U.S. territorial possession from 1903-1979, passed over to the nation of Panama by way of the Torrijos-Carter Treaty.
Empire By Default discusses the former in quite a bit of detail; and Edmund Moriss' biography of Teddy Roosevelt give a solid accounting of the acquisition of the latter.
What about the Philippines' independence from the United States in 1946? Or are you just looking for land lost that had joined the Union as a state?
I'm not sure of the total +/- with this treaty but maybe we lost land overall with the Webster-(ashleby??) Treaty that solves us Canada border disputes.