Cell CAM 105 (C-CAM) is a member of the carcinoembryonic antigen family and has been characterized as a rat hepatocyte cell-cell adhesion molecule via antibody activity. Two isoforms have been cloned and differ primarily in the length of the cytoplasmic domain. Despite extensive structural studies, little is known about their function and regulation in vivo. We have examined C-CAM expression during rat liver regeneration and hepatocarcinogenesis. Steady-state C-CAM RNA varied less than 3-fold during regeneration with subtle changes in the isoform ratio both before and after hepatocyte division. In liver tumors and transformed cells derived from tumors, however, largescale decreases were observed in C-CAM RNA with wide variations in isoform ratios. In general, RNA decreases were reflected at the protein level. Our data suggest whereas down-regulation and alterations in C-CAM isoform ratio are transient during regulated liver growth, they are permanent in malignancy and may modulate hepatocyte adhesion.