A method for protein structure determination from two-dimensional NMR cross-relaxation data is presented and explored by using short amino acid segments from acyl carrier protein as a test case. The method is based on a molecular mechanics program and incorporates NMR distance constraints in the form of a pseudoenergy term that accurately reflects the distance-dependent precision of NMR cross-relaxation data. When it is used in an indiscriminant fashion, the method has a tendency to produce structures representing local energy minima near starting structures, rather than structures representing a global energy minimum. However, stepwise inclusion of energy terms, beginning with a function heavily weighted by backbone distance constraints, appears to simplify the potential energy surface to a point where convergence to a common backbone structure from a variety of starting structures is possible. In the case of the segment from residues 3 to 15 in acyl carrier protein, a nearly perfect .alpha.-helix is produced starting with a linear chain, an .alpha.-helical chain, or a chain having residues with alternating linear and .alpha.-helica backbone torsional angles. In the case of the segment from residues 26 to 36 a structure having a right-handed loop is produced.