The expression of human cellular fibronectin (HFN) was analyzed in relation to the differentiation process of the human enterocyte-like cell line Caco-2. A single approximately 290-kDa form of HFN, corresponding to a 10.0-kb mRNA species, was observed in Caco-2 cells. The expression levels of both protein and mRNA were found to decrease to undetectable levels concomitantly to the differentiation process of these cells. This decline in HFN expression was correlated with the expression of sucrase-isomaltase (a specific marker of intestinal cell differentiation). These results indicate that intestinal epithelial expression of HFN is down-regulated through its mRNA levels and is correlated with the acquisition of the differentiated enterocytic phenotype.