The majority of the 136 letters in the series were composed by Benjamin Rush, and letters he wrote to Julia during the 1793 yellow fever epidemic in Philadelphia form a substantial part of the series. Main topics in the letters include Rush family matters, medical treatments for a wide variety of medical issues, American politics, and the country's relations with European nations. Other topics include mental illness and its treatment, the medical department in the Continental Army, the impact of epidemics upon commerce internationally, reading habits, parenting, and capital punishment.
Among the prominent correspondents who wrote one or more personal or professional letters to Rush or his wife are Abigail Adams, John Quincy Adams, Thomas Jefferson, James Madison, Thomas Paine, and George Washington. Letters from others to Julia Rush seek to continue ties with her and the Rush family, and offer condolences following Benjamin's death. Included are several manuscript copies Benjamin Rush made of individual letters he penned.