Inadequate reactions of the immune system, i.e. allergic or hypersensitivity reactions, can lead to lung tissue injury. We investigated the relationship of type IV hypersensitivity, as an example of IgE independent hypersensitivity, with the induction of airway hyperreactivity. After antigen challenge (picrylsulphonic acid (PSA] in picrylchloride (PCl) sensitized mice, peribronchial and perivascular accumulation of mononuclear cells was found that was maximal 48 h after challenge. At several time points after challenge, changes in smooth muscle tone of mouse isolated tracheas were measured isometrically. In sensitized mice the response to carbachol was increased, reaching a maximum 48 h after challenge. This hyperreactivity was not found in athymic (nude) mice. We concluded from these data that airway hyperreactivity can be immunologically induced other than by IgE.