X‐Ray diffraction studies and energy‐minimization calculations were carried out on two dipeptides, N‐tosyl‐l‐Ser‐Gly‐OMe monohydrate (C13H18N2O6S·H2O, compound A) and N‐tosyl‐l‐Thr‐Gly‐OMe (C14H20N2O6, compound B). Compound A crystallized in the monoclinic system, space group P21 with unit cell parameters a= 4.915(1), b= 15.625(4), c= 11.003(1) Å, β= 91.28(1)°, V= 844.8 Å3. Mr= 348.4, d= 1.37(2) g cm−3, Z = 2, λ(Cu Kα) = 1.5418 Å, μ= 1.99 mm−1, T=293 K. R= 0.032 for 1451 unique reflections with I > 2σ(I). Compound B crystallized in the orthorhombic system, space group P212121, with unit cell parameters a= 5.050(2), b= 16.483(3), c= 20.769(5) Å, V= 1729.3 Å3, Z = 4. Mr= 344.4, d= 1.32(2) g cm−3, μ(Cu Kα)= 1.90 mm−1. R= 0.040 for 1060 unique reflections with I > 2σ(I). The major difference in the backbone conformation of the two compounds is in their glycine residues, with the glycine residue in compound A adopting an extended conformation with φ= ‐ 132.6(3)° and ψ= 175.3(3)° and that in compound B having a folded conformation with φ=−56.3(6)° and ψ=−42.6(7)°. In compound A the oxygen atom of the Ser side‐chain and the carbonyl oxygen atom of glycine are bridged by the water of crystallization through O—H ··· O hydrogen bonds, resulting in the relatively rare trans conformation [χ=− 175.7(2)°] for this side‐chain. The Thr side‐chain in compound B is in the sterically preferred (tg−) conformation [χ1,1=− 179.4(4)° and χ1,2=−62.3(5)°]. The conformations were found to be in general agreement with those obtained by an energy‐minimization procedure. The energy‐minimized structure of N‐tosyl‐l‐Ser‐Gly‐Ome (anhydrous) showed a strong hydrophobic interaction between the methyl substituents of the tosyl group and the methyl ester (C—C = 4.08 Å). Copyright © 1993, Wiley Blackwell. All rights reserved