Adenylate cyclases (ACs) are involved in signal transduction by generating the second messenger, cAMP. In Trypanosoma brucei, 3', 5'-cyclic adenosine monophosphate (cAMP) controls the life cycle of this unicellular parasite. cAMP is generated by a class of adenylate cyclases which are either constitutively (GRESAG4.1-4.3) or transiently expressed (ESAG4) during the life cycle. Unlike mammalian ACs, the trypanosomal ACs have a simple topology comprising of a large extracellular region, a transmembrane helix and a cytosolic catalytic region. Two orthorhombic crystal forms of the catalytic AC domain of GRESAG4.1 (residues Ala884-Thr1132) were generated by the hanging-drop vapour-diffusion method. X-ray diffraction data from GRESAG4.1 crystals were collected at 1.9 A resolution using synchrotron radiation. Furthermore, two heavy-metal derivative data sets were collected from crystal form A; heavy-atom sites were subsequently located in difference Patterson maps.