The Guyot Collection consists of 61 letters written by Louis Agassiz (15 items), his wife Elizabeth (32), and their son Alexander (14), to their friend and fellow naturalist, Arnold Guyot. Primarily personal in nature, the letters reflect a long and intimate friendship, making frequent mention of family and mutual friends. There is, however, comparatively little in the collection relating to their respective scientific endeavors, with only a few references to the situation at the Museum of Comparative Zoology and at Princeton, to publications of various sorts, to the difficulties of their mutual friend Leo Lesquereux, and to other colleagues.

Letters from both Louis and Alexander are written in French, while Elizabeth's are in English.