Shigella sonnei infection resulting from oral administration of 500 colony-forming units was followed in 11 volunteers with the objective of studying the immune response and pathogenesis. Characterization of infection included recording of signs and symptoms, excretion of S. sonnei in stool, measurement of humoral tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma), C-reactive protein, IL-2 receptor, soluble CD8, antibody-antigen complexes, and endotoxin. Measurements were also made of the immune response including lymphocytes secreting antibody to S. sonnei O antigen and serum antibody to this antigen. Six of the volunteers developed typical shigellosis with excretion of bacteria in stool and systemic signs and symptoms, three excreted bacteria but did not show illness, and two showed no evidence of infection or illness. Shigellosis was characterized by excretion in stool of S. sonnei beginning on average 1.3 days after ingestion. Excretion of S. sonnei (mean of time of the first positive cultures) was followed in sequence by the onset of increases in TNF-alpha (10 hr), liquid stools (14 hr), fever and dysentery (18 hr), IFN-gamma (22 hr), and C-reactive protein (34 hr). A S. sonnei-specific immune response was demonstrated somewhat later, between days 4 and 7 postinfection by antibody-secreting cells, and between days 7 and 14 postinfection by humoral antibody. Shigellosis was not associated with increased humoral IL-1 beta, endotoxin, or antigen-antibody complexes.