AbstractImmunoproliferative small intestinal disease (IPSID), most common in Mediterranean countries, is characterized by lymphomatous infiltration of the small intestine and is usually associated with the synthesis of anomalous immunoglobulin alpha heavy chains. Flow cytometric analysis of DNA content, S phase fraction, and quantitative analysis of the proliferation‐associated nuclear antigen, P105, were performed in 23 patients with IPSID to determine if they could be used as prognostic indicators in this disease. Eighteen patients had low‐grade, two had intermediate‐grade, and three had high‐grade lymphoma. Eight patients had clinical stage IE disease, 12 had stage IIE, and three had stage IIIE disease. Eleven patients survived>5 yr (good prognosis), four survived between 2–5 yr (intermediate prognosis), and eight survived 2 yr or less (poor prognosis). The S phase fraction of patients with poor prognosis was significantly higher than those with intermediate or good prognosis (P<0.004). Flow cytometric evaluation of S phase fraction may offer important prognostic information in patients with IPSID and could be useful in the clinical management of patients with this highly variable clinical syndrome. Further studies evaluating the value of DNA flow cytometry in larger groups of patients with IPSID are warranted. © 1995 Wiley