Volume 14 contains letters for 1866, a year marked by the deaths of two of Darwin's sisters, when Darwin submitted the manuscript of Variation under Domestication to his publisher, and began thinking about a work dealing specifically with the controversial subject of human evolution.

Charles Darwin's health improved substantially in 1866 under a dietary and exercise regime prescribed by his physician Henry Bence Jones. With renewed vigour, he worked steadily on his manuscript of Variation of Plants and Animals under Domestication, submitting all but the final chapter to his publisher in December. He also worked on the fourth, and much revised, edition of Origin which was delivered to printers in July, and preparations were begun for a third German edition of Origin. His improved health allowed him a more active social life. At Down, Darwin entertained a number of scientific colleagues whom he had known previously only through correspondence. He also made his first appearance in London scientific society in many years, touring the Zoological Gardens at Regent's Park, and appearing at a soirée at the Royal Society.