D,L-Histidyl-L,D-histidine pentahydrate, C12H16-N6O3.5H2O, Mr = 382.38, F(000) = 408, crystallizes in the monoclinic space group Pc with the cell dimensions a = 9.971 (2), b = 4.745 (2), c = 19.572 (3) A and beta = 96.08 (1) degree, V = 920.6 A3, Z = 2, D chi = 1.379 g cm-3. mu = 1.083 cm-1, T = 295 K, Mo K alpha, lambda = 0.71073 A. Final R (on F) = 0.040 for 1658 observed reflections with I greater than or equal to 3 sigma (I). This dipeptide crystallizes in a zwitterionic form with protonation of the C-terminal imidazole ring. Both histidine units exist in the g+ or 'closed' conformation with C alpha-C beta torsion angles of 67.2 (3) and 63.6 (3) degrees. Principal torsion angles, omega = 176.8 (2). psi 1 = 161.8 (3) and phi 2 = -152.1 (3) degrees, are indicative of a highly extended trans conformation. Intramolecular hydrogen bonding occurs between the imidazole rings [N2D-H2D1...N1D = 2.724 (4) A]. Intermolecular hydrogen bonding occurs between symmetry-related histidine molecules forming chains along the gamma axis and includes another short [2.764 (4) A] N-H...N interaction. The five water molecules occupy channels between adjacent histidine layers.