Indirect immunofluorescence studies were performed to determine whether the antigenic recognition by Crohn's disease (CD) sera of lymphoid tissue from nude (nu/nu) mice injected with CD filtrate is related to cell wall defective pseudomonas-like bacterial revertant forms (CWD-RF). Antisera raised in rabbits against two CWD-RF isolates from CD tissues did not stain lymphomas or hyperplastic lymph nodes produced by CD filtrates, although these tissues demonstrated positive immunofluorescence with CD sera. Pre-absorption of reactive CD sera with CWD-RF did not block this immunofluorescence. Formalinized suspensions of CWD-RF were injected into 36 nu/nu, 12 nu/+, and 31 conventional mice. Thirty other mice were fed suspensions of bacteria. Several nu/nu injected with CWD-RF developed lymphoma (n = 2) and plasma cell hyperplasia (n = 5), none of which reacted with CD sera. Mice fed bacteria did not show intestinal pathology. These studies demonstrate that CWD-RF are not directly related to lymphomagenesis in nu/nu induced by CD filtrates and that different CD serum antibodies are involved in recognition of CWD-RF and lymphoid tissues from nu/nu previously injected with CD filtrates.