The diversity of cytodifferentiation in a transplantable rat pancreatic acinar carcinoma provides a biological model system for the study of regulatory molecular events that differ from those in normal acinar cells. Secretory (zymogen) granule proteins and granule membranes of neoplastic and normal pancreatic acinar cells were compared to determine the differences in gene expression between apparently well-differentiated secretory granule-containing neoplastic cells and normal cells. Nineteen proteins observed in two-dimensional polyacrylamide gels of normal secretory granule extracts were seen also in tumor granule extract profiles, with reduced but detectable amounts of lipase and four basic proteins. In addition, tumor granule extracts contained a new protein of Mr 24,000, designated p24, which was not detectable in normal extracts. Neoplastic granule membranes, while having phospholipid composition similar to that of normal membranes, lacked or contained a greatly reduced amount of a major glycoprotein of Mr 80,000 and three other proteins of Mrs 50,000, 37,000, and 36,000. The nature of p24 protein in secretory granule extracts and the significance of the reduction or absence of Mr 80,000 membrane glycoprotein in this tumor remain to be elucidated.