Many organisms contain proteins which regulate the size and shape of inorganic crystals in their skeletal elements, most likely through specific protein-crystal surface interactions. As a model for better understanding such control of crystal morphology, an a-helical peptide (CBP1) was synthesized having an array of aspartyl residues designed to bind to the {110} prism faces of calcite. When added to a saturated solution of calcium bicarbonate containing rhombohedral calcite seed crystals, CBP1 had a remarkable effect on subsequent calcite growth, depending on growth conditions. At 3 degrees C, where CBP1 is 89% helical, the crystals assumed a prismatic habit, with growth continuing along the c-axis, but inhibited parallel to the c-axis and prism faces; at 25 degrees C, where CBP1 is largely unstructured, studded crystals formed, resulting from epitaxial growth off each of the six rhombohedral surfaces. Other acidic peptides also caused similar epitaxial growth. These results suggest that the helical form of the peptide recognizes specific crystal surface characteristics, whereas the unfolded form acts nonspecifically as a polyanion. When the peptide was removed from the growth medium containing either type of crystal, regrowth of {104} rhombohedral surfaces ensued at the expense of the nonrhombohedral surfaces. These results represent the first example of conformation-dependent control of calcite crystal growth by a peptide of defined secondary structure.