The build-up procedure for predicting low-energy conformations of polypeptides has been extended to cover the case of peptides in aqueous solutions. The revised procedure consists of five steps to be applied to each stage of the build-up. I. All low-energy minima of each of the two fragments to be joined are combined as starting points for energy minimization of the enlarged fragment, and those minima of the enlarged fragment within a certain upper bound of the lowest energy are retained. 11. Whenever one of the combinations in Step I leads to an atomic overlap, the minimization is started again using a pseudoenergy function which remains finite everywhere and becomes equal to the standard energy function when no atoms overlap. 111. The minima generated in Steps I and I1 are culled by ignoring side-chain conformations and retaining only those minima whose backbone conformations differ significantly. IV. The rotameric states of the side chains are optimized, by testing their energy of interaction with the rest of the molecule, and subjecting the whole molecule to a further round of energy minimization if the test indicates that this would reduce the energy. V. The energies of all minima are recomputed with inclusion of a term for solvation and with a smaller upper bound as the criterion for retention. The original build-up procedure consisted of Steps I and I11 only. Examples are presented showing the effectiveness of the new Steps I1 and IV in locating low-energy minima, and the problems that remain to be solved, chiefly concerning Step V, are discussed.