Selective lipid transport through the brush-border membrane in the small intestine of mammals is mediated by membrane-bound proteins, the so-called scavenger receptors of class B, type I or II (SR-BI or -BII). These, in turn, are inhibited by certain proteins and synthetic a-peptides that have an amphipathic helix as the binding motif (Fig. ). In whole cells (test with human colonic carcinoma cells, CaCo-2), on the other hand, the inhibitors are subject to proteolysis. We have now tested six b-peptides (hexa-, hepta-, and nonamers 1 ± 6), each carrying one to seven water-solubilizing side chains of either Ser or Lys, with a brush-border-membrane (BBM) vesicle model system (rate and IC 50 values in Figs. and) and with a tightly packed monolayer of CaCo-2 cells (rate in Fig. ), to find that the rate of transport of cholesterol can be reduced to what may be considered the passive diffusion (background) level. There is a correlation between the ability of the b-peptides to form an amphipathic-type 3 14 -helical secondary structure in MeOH and their inhibitory effect (Table and Fig. ). Although the inhibitory activity of the b-peptides is in only the mm range (Table ), it is to be compared with no activity at all of previously tested a-peptides and proteins (built of l-amino acids) in CaCo-2 cells. Furthermore, these active b-peptides (1, 5, and 6) contain only seven or nine residues and must be considered simple, first-generation models capable of mimicking the biological activity of amphipathic a-peptide helices in living whole cells.