Background and Purpose: Sendai virus infection in rats is an excellent model for studying development and role of host defenses throughout the respiratory tract after this infection. Therefore, development of serum antibody responses and disease were studied. Methods: Forty-two anesthetized pathogen-free 3- to 4- week-old LEW/NCr rats were inoculated intranasally with Sendai virus. At postinoculation days 0, 2, 3, 5, 8, 10, and 14, rats were euthanized by administration of a pentobarbital sodium overdose followed by exsanguination. Serum was obtained from all animals, and nasal wash and bronchoalveolar lavage specimens were collected during selected experiments. An ELISPOT assay was used to measure numbers of Sendai virus-specific antibody-forming cells in respiratory tract lymphoid tissue. Results: Recovery from disease and clearance of virus from respiratory tract tissues coincided with development of serum antibody responses. Upper respiratory tract lymph nodes were the initial and major sites of appearance of antibody- forming cells. Immunoglobulin G was the predominant subtype of these cells during recovery from the infection and in rats resistant to infection. Passive transfer of antisera or specific IgG protected the lower but not the upper respiratory tract. Conclusions: Circulating components of immunity have a major role in resistance and recovery from disease in the lower respiratory tract, whereas local responses are likely involved in protection of the upper respiratory tract. Local lymphoid tissues are the major production sites of IgG, which contributes to resistance to and recovery from respiratory tract diseases.