Resistance to cutaneous syphilitic reinfection in strain 2 and strain 13 guinea pigs developed gradually 3 to 7 months after primary infection and reached maximum levels at 6 to 7 months after the induction of primary cutaneous disease. Associated with this acquired resistance was the occurrence of Arthus reactions and anamnestic-type antibody responses. Passive transfer of immune serum containing high-titered treponemal antibody into normal strain 2 guinea pigs significantly delayed the appearance and markedly diminished the severity and duration of skin lesions that developed after these recipients were challenged with treponemes but did not prevent the dissemination of organisms to the draining lymph nodes. These findings provide direct evidence that syphilitic infection elicits the formation of serum factors that are, at least, partially protective against symptomatic disease.