Two cases of yellow fever vaccine-associated viscerotropic adverse events (YEL-AVD) were identified by review of correspondence received at the Centers for Disease Control and Prevention (CDC; Ft. Collins, CO). The cases occurred in Indiana and Maryland in 1973 and 1978, respectively. One patient, a 75-year-old man with multi-organ failure died, and the other, a 31-year-old woman, was hospitalized for 14 days. Onset was 3-6 days after vaccination. The illness was characterized by fever, headache, myalgia, gastrointestinal symptoms, hepatic and renal dysfunction, and (in the fatal case), shock and coagulopathy, compatible with YEL-AVD. Liver pathology showed diffuse, spotty necrosis, acidophilic degeneration, Kupffer cell hyperplasia, and microvesicular fat. No virological confirmation was obtained, so that both cases remain classified as "suspect." The 1973 case is the earliest record of YEL-AVD; until now, the earliest known case of YEL-AVD had been in 1975 in Brazil, and most subsequent cases have been reported after 1995.