We describe the solution ('H-nmr) and calculated conformations of the opiatelike peptide dermorphin and the analysis of structure-conformation-activity relationships in the series [Alan]dermorphin. We used 'H-nmr spectroscopy to study dermorphin and its analogs [Alan]dermorphin (with n = 1, 2...7) dissolved in dimethylsufoxide. Conformational energy calculations using semiempirical partitioned energy function methods were then carried out on dermorphin and its [~-Ala~]-analog. Agreement between calculation and experiment is satisfying, both suggesting predominance of a type I p-turn around Pro6-Ser7 at the Gterminus and of an extended structure in the central sequence Phe3-Gly4-51.5. Detailed analysis by step-by-step substitutions with Ala indicates that intraresidue interactions dominate over medium-range interactions (between adjacent residues), although the latter may also have a noticeable influence in shaping conformations. As a general feature, the effects of substitutions on the arrangement of side chains are always larger on the succeeding residue than on the preceding residue. Almost all the variations of activity observed in the analogs can be explained from conformational changes occurring in the aromatic side chains of the biologically important Tyr', Phe3, and Tyr5 on substitutions effected on adjacent residues (fluctuations via medium-range interactions).