The two prominent nineteenth-century neurophysiologists/neurologists C.E. Brown-Séquard and S.W. Mitchell maintained an active correspondence during their careers. These letters, never before studied as a unit, provide insight into the men's close collegial association in several domains. They shared camaraderie as pioneer physiologists who tried to bring experimental discoveries from the laboratory to the clinical setting. They critiqued each other's research and facilitated its publication in journals over which they had influence. Through letters of recommendation, they also helped foster each other's local careers. In a period of transition in neuroscience from a traditional anatomic focus to the emerging predominance of neurophysiology and neuropharmacology, their correspondence documents the views of two late nineteenth-century leaders in science and international academic medicine.