I. One of the most interesting developments in our knowledge of gastric mucosal pathobiology has been the recognition of the relationship between Helicobacter infection, chronic gastritis, induction of lymphoid follicles in the mucosa (MALT)C and gastric lymphoma. Difficulties in distinguishing histologically between florid reactive lymphoid hyperplasia, sometimes termed "pseudolymphoma," and lymphoid neoplasia have long been recognized. More recently, monoclonality of lymphoid proliferations and the presence of gene rearrangements have been taken as evidence of transformation to a neoplastic state, and molecular techniques have increased our sensitivity over histology in detecting these lesions. However, the demonstration by Isaacson's group, subsequently confirmed by others, that early MALT lymphomas, diagnosed by morphologic and molecular criteria are not autonomous but are driven by specific Helicobacter antigens in the presence ofT cells and regress upon elimination of the Helicobacter infection, is both intriguing and important [1, 2]. First, it has altered our management of patients with early MALT lymphomas of the stomach. Second, it raises as yet unanswered questions about the longterm outcome of these lesions: for example, following regression of the initial tumor, does a population of "tumor" cells remain in the mucosa with the potential for re-emergence if the bacterium is incompletely eradicated or if reinfection occurs, as a few early reports suggest . How can we distinguish reliably between "early" or antigen-dependent lymphoid proliferations and those that are truly autonomous and that, therefore, will not respond to antibiotic therapy? Moreover, it prompts a semantic question concerning the definition of neoplasia: recognizing that its development is a multi-step process, how do we now define when neoplastic transformation has occurred in this setting? Are these early MALT "lymphomas" true neoplasms, or are they merely reactive monoclonal lymphocytic reactions to a persistent foreign antigen, best defined as pre-neoplastic? Finally, it raises fundamental questions as to what molecular changes occur in mucosal B-cells during the progression from reactive gastritis to low-grade and high-grade maltoma and how Helicobacter pylori elicits them. The availability of a mouse model of Helicobacterinduced gastric maltomas offers an opportunity to compare the roles of products generated by Helicobacter and those produced by inflammatory cells in a similar system . In association with studies on readily accessible human gastric biopsy tissue, this may lead to elucidation of the pathogenesis of this interesting lymphoproliferative process.