Specific-pathogen-free 10-week-old chickens were inoculated via the air sac with Escherichia coli and showed lymphocytic depletion of bursa of Fabricius and thymus. In experiment I, chickens were necropsied at 12 and 24 hours, 2, 3, and 5 days after inoculation. At 12 hours after inoculation there was lymphocytic depletion in the medulla of lymphoid follicles of the bursa. At 24 hours after inoculation there was lymphocytic depletion also in the cortex of follicles and edema in interfollicular interstitium and follicular medulla. At 2 and 3 days after inoculation there were more marked lymphocytic depletion in medulla and cortex, and fibrosis in interfollicular interstitium. Partial repopulation of follicles with lymphocytes was seen at 5 days after inoculation. In the thymus, lymphocytic depletion occurred in the cortex. At 12 hours after inoculation, lymphocytic necrosis increased in number more than that of control chickens. The width of the cortex and medulla decreased. At 24 hours after inoculation, lymphocytic necrosis increased further. At 2 to 5 days after inoculation, the boundary between the cortex and medulla of lobules was obscure and cellular elements of the cortex and medulla were mingled. In experiment II, chickens were necropsied as in experiment I and also at 8 and 14 days after inoculation. The relative weights of the bursa and thymus reduced rapidly to minimal relative weights at 8 days after inoculation. At 14 days after inoculation, both bursa and thymus had normal relative weights and histological structures. These findings indicate that E. coli infection may induce transient lymphocytic depletion of lymphoid tissues in the chicken.