In the preceding paper (Paulweber, B., Onasch, M. A., Nagy, B. P., and Levy-Wilson, B. (1991) J. Biol. Chem. 266, 24149-24160) we demonstrated that the segment of the apolipoprotein B promoter extending from -260 to -85 is functionally different in hepatic (HepG2) and intestinal (CaCo-2) cells. These functional differences could be explained at least in part by differences in binding of three nuclear proteins to the region from -111 to -88. In this article we present further evidence suggesting that the mechanisms involved in transcriptional control of the apolipoprotein B gene in HepG2 and CaCo-2 cells are different, by demonstrating that an enhancer and a reducer can alter the activity of various apolipoprotein B promoter segments in widely differing ways in these two cell lines. Furthermore, we have localized a 329-base pair segment that is found within a negative regulatory region in the 5' distal portion of the gene. It displays a strong reducer effect upon promoter sequences that exhibit maximal transcriptional activity in CaCo-2 cells, but not in HepG2 cells.