This volume's 598 documents span 22 April 1818 to 31 January 1819. Jefferson spends months preparing for a meeting to choose the site of the state university. He drafts the Rockfish Gap Report recommending the location of the University of Virginia at Charlottesville as well as legislation confirming this decision. Jefferson travels to Warm Springs to cure his rheumatism but instead contracts a painful infection on his buttocks. His enforced absence from Poplar Forest leads to detailed correspondence with plantation manager Joel Yancey. A work that Jefferson helped translate, Destutt de Tracy’s Treatise on Political Economy, is finally published. Salma Hale visits Monticello and describes Jefferson’s views on food, wine, and religion. In acknowledging an oration by Mordecai M. Noah, Jefferson remarks that the suffering of members of the Jewish faith "has furnished a remarkable proof of the universal spirit of religious intolerance." He receives long discussions of occult science and the nature of light by Robert Miller and Gabriel Crane. Abigail Adams dies, and Jefferson assures John Adams that their own demise will result in “an ecstatic meeting with the friends we have loved & lost and whom we shall still love and never lose again.”

This volume’s 571 documents cover both Jefferson’s opposition to restrictions on slavery in Missouri and his concession that “the boisterous sea of liberty is never without a wave.” Seeking support for the University of Virginia, he fears that southerners who receive New England educations will return with northern values. Calling it “the Hobby of my old age,” Jefferson envisions an institution dedicated to “the illimitable freedom of the human mind.” He infers approvingly from revolutionary movements in Europe and South America that “the disease of liberty is catching.” Constantine S. Rafinesque addresses three public letters to Jefferson presenting archaeological research on Kentucky’s Alligewi Indians, and Jefferson circulates a Nottoway-language vocabulary. Early in 1821 he cites declining health and advanced age as he turns over the management of his Monticello and Poplar Forest plantations to his grandson Thomas Jefferson Randolph. In discussions with trusted correspondents, Jefferson admires Jesus’s morality while doubting his miracles, discusses the materiality of the soul, and shares his thoughts on Unitarianism. Reflecting on the dwindling number of their old friends, he tells Maria Cosway that he is like “a solitary trunk in a desolate field, from which all it’s former companions have disappeared.”

The 637 documents in this volume span 1 February to 31 August 1819. As a founding member of the University of Virginia Board of Visitors, Jefferson helps to obtain builders for the infant institution, responds to those seeking professorships, and orchestrates the establishment of a classical preparatory school in Charlottesville. In a letter to Vine Utley, Jefferson details his daily regimen of a largely vegetarian diet, bathing his feet in cold water each morning, and horseback riding. Continuing to indulge his wide-ranging intellectual interests, Jefferson receives publications on the proper pronunciation of Greek and discusses the subject himself in a letter to John Adams. Jefferson also experiences worrying and painful events, including hailstorm damage at his Poplar Forest estate, a fire in the North Pavilion at Monticello, the illness of his slave Burwell Colbert, and a fracas in which Jefferson's grandson-in-law Charles Bankhead stabs Jefferson's grandson Thomas Jefferson Randolph on court day in Charlottesville. Worst of all, Jefferson's financial problems greatly increase when the bankruptcy of his friend Wilson Cary Nicholas leaves Jefferson responsible for $20,000 in notes he had endorsed for Nicholas.