Until now and based on the success of the helix/coil transition theory it has been assumed that the alpha-helical propensities of the amino acids are position independent. This has been critical to derive the set of theoretical parameters for the 20 natural amino acids. Here, we have analyzed the behavior of several non-polar residues, Val, Ile, Leu, Met and Gly at the N-cap, at each position of the first helical turn and at a central helical position of a 16-residue peptide model system that starts with eight consecutive alanine residues. We have interpreted the results from these experiments with the model of the helix/coil transition (AGADIR), that indicates that the intrinsic helical propensity is position dependent. Gly, Val and Ile are more favorable at the first turn than in the middle of the alpha-helix, while for Leu and Met we observe the opposite behavior. The differences between the observed helical propensities are as large as 1.0 kcal/mol in some cases. Molecular modeling calculations using the ECEPP/2 force-field equipped with a hydration potential show that this effect can be explained by the combination of three factors: (a) the side-chains in the first helix turn are more solvent-exposed; (b) they have fewer intramolecular van der Waals' contacts; and (c) they posses higher configurational entropy than that in the central position of an alpha-helix. The position-dependent results of the calculations are in reasonable agreement with the experimental estimates and with the intrinsic propensities of the amino acids derived from the statistical analysis of the protein structure database. Copyright 1998 Academic Press Limited.