The primary structure of smooth muscle caldesmon and calponin was screened for the presence of amphiphilic alpha-helices which can participate in the formation of protein-lipid contacts. Only one caldesmon segment (residues 645-660) having a predominantly alpha-helical structure and high hydrophobic moment satisfies all criteria for a surface-seeking helix and is predicted to be involved in the caldesmon-phospholipid interaction. This prediction agrees with experimental results indicating that one of the caldesmon-phospholipid binding sites is located in the sequence 628-658 [Bogatcheva et al. (1994) FEBS Lett. 342, 176]. Two segments of calponin (residues 45-55 and 85-95) exhibit high hydrophobic moments and the sequence 85-95 is characterized by a high probability of alpha-helix formation. This may suggest that at least one of these segments could facilitate the calponin-phospholipid interaction and that calponin, as with many other actin binding proteins, is able to interact with membranes.