We are conducting studies designed to define the cellular basis for the appearance and accumulation of specific antibody-forming cells (AFC) in lung parenchyma of mice after intrapulmonary deposition of sheep erythrocytes (SRBC). This study was performed: (1) to compare qualitatively the AFC responses to intratracheally administered antigen among unprimed mice and among mice primed either by adoptive transfer of sensitized lymphocytes or by systemic immunization, and (2) to define quantitatively the relationship between the appearance of AFC in hilar lymph nodes (HLN) and in lung parenchyma in these 3 groups of mice. Both antigen dose-response and kinetic analyses of the appearance of AFC in the HLN and lung parenchyma were performed. There was a direct relationship between the dose of SRBC administered intratracheally and the magnitude of the AFC-responses in HLN and lungs; AFC appeared in HLN at substantially lower intratracheally administered doses of SRBC than in lungs. The major effect of adoptive transfer or of systemic priming was to shift the dose-response curves significantly to the left, such that AFC appeared in HLN and lungs at lower antigen doses than in unprimed mice. Kinetic analyses showed that the initial appearance and the peak concentrations of AFC occurred earlier in HLN than they did in lung parenchyma. Priming shifted the kinetic curves to the left, accelerating the appearance of AFC; the sequential relationship between AFC appearance in HLN and in lungs was preserved. These observations indicate that: (1) the responses of unprimed, adoptively transferred, and systemically primed mice to intratracheally administered antigen are qualitatively similar, but differ quantitatively in the magnitude of the antigen dose required to elicit AFC in HLN and lung, and (2) after intrapulmonary deposition of antigen, immune responses are generated initially in extraparenchymal lymphoid tissue; AFC appear secondarily in lungs. This model provides a quantitative method for defining the effect of environmental agents or of lung disease on the immune reactivity of the lung.