US-56 lies directly on the route of the Oregon-California and Santa Fe trails, near a place where the trails branched, with one road pointing northwest to Oregon and another southwest to Santa Fe. Between 1840 and 1870 thousands of settlers, miners, and soldiers traveled the 2,000 miles of the Oregon-California Trail from the "jumping off" towns on the Missouri River to the Pacific Ocean. Their greatest enemies were diseases such as cholera and smallpox, and unknown thousands of emigrants died from disease, as did many of the Indians through whose lands they traveled. The Santa Fe Trail became famous as a freight route between Missouri and New Mexico; pack trains made the difficult journey as early as 1821, following rivers and earlier Indian trails, and by 1825 large wagon trains were carrying tons of goods both east and west. US-56 generally follows the old trail route southwestward across Kansas for some 500 miles, nearly two-thirds of the trail's total length.