Experiments to determine whether Ixodes scapularis can be infected with the Lyme disease agent, Borrelia burgdorferi, demonstrated that infection and transstadial transmission occurs in up to 73% of larval ticks that had fed on spirochetemic rabbits. In a limited number of nymphal ticks examined, the spirochetes were found only in the midgut. Feeding nymphal I. scapularis on a normal rabbit resulted in blood infection characterized by two distinct periods of spirochetemia, suggesting the occurrence of a relapse phenomenon similar to that in tick-borne relapsing fevers. This was also indicated by the percentage of infected ticks recovered daily during the experiment. Accordingly, ticks fed during low spirochetemias or negative blood phase, showed low infection rates or were not infected whereas those fed during peak spirochetemias had high infection rates. Of 11 adult I. scapularis examined to date, 6 were infected but the spirochetes were restricted to the midgut. These preliminary findings establish the susceptibility of I. scapularis to B. burgdorferi and the potential role of this tick as an efficient vector of the Lyme disease spirochete.