He stood by Mr.Clay against the Southern Democrats in the angry contest of 1850, declaring that "if the Union must be dismembered" he "prayed God that its ruins might be the monument of his own grave." He "desired no epitaph to tell that he survived it." Against the madness of repealing the Missouri Compromise he entered a protest and a warning.

He notified his Southern friends that the dissolution of the Union might be involved in the dangerous step.

He alone, of the Southern Democrats in the Senate, voted against the mischievous measure.

When three thousand clergymen of New England sent their remonstrance against the repeal, they were fiercely attacked and denounced by Douglas and by senators from the South.

Houston vindicated their right to speak and did battle for them with a warmth and zeal which specially commended him to Northern sympathy.