Because of ill health, he retires from military service, in 1796, and lives at Mulberry Hill, to help his brother, the general, in business matters.

In July, 1803, accepts an offer from his friend and fellow officer, Captain Meriwether Lewis, requesting his company and assistance on an exploring trip up the Missouri River, through the Province of Louisiana, for the Government.

Is commissioned by President Jefferson second lieutenant of artillerists.

In October, 1803, he leaves with part of the expedition for St. Louis.

1804—1805—1806 is engaged in exploring to the Pacific Ocean and back. The Indians name him the Red Head.

1806, resigns his commission in the army.

1807, appointed by President Jefferson brigadier-general of the militia of Louisiana Territory and Indian agent for the Territory. Is very popular with the Indians, who revere his justness and honesty.

In 1808 marries Julia Hancock.

In 1813 is appointed governor of the Territory of Missouri.

In 1821 marries Harriet Kennerly-Radford, but is defeated in his candidacy for the governorship of the new State of Missouri.