Chapter 1. Production of crystals for diffraction analysis would be assisted by the devising of a set of rules which, given molecular formula, could predict crystal formation conditions. By studying trends in structural properties of a group of closely related simple molecules, deductions could be drawn which could then be applied more generally. Chalcone derivatives with minor substituent differences were recrystallised. X-ray diffraction data collected and the structures solved and refined. Additionally, NMR and UV studies were performed, investigating an observed dimerisation reaction. Chapter 2. Discovery of peptide hormones and neurotransmitters has stimulated the study of structure-activity relationships, although the structure of these molecules is often poorly defined. Proctolin, a linear pentapeptide, is a neurotransmitter in insects. Crystallisation was attempted, with the aim of deducing the active conformation structure, thereby assisting in design of small molecule analogues for use as non-cholinergic pesticides. No diffraction was observed from the crystals produced. Chapter 3. Glucosamine 6-phosphate synthase is an N-terminal nucleophile amidotransferase catalysing the first step in the hexosamine pathway, from which all amino-sugar containing macromolecules are derived. Structure determination of each of two subdomains was attempted. In one case, pseudo-symmetry appeared to obstruct structure solution. The symmetry has subsequently been understood and the structure obtained. Crystals of the second domain are rotationally disordered. Chapters 4 and 5. Recent advances in macromolecular crystallographic techniques have facilitated the collection of an increasing number of high quality, atomic resolution data sets. Methods for refinement, previously limited to small molecule structures, have increasing relevance for proteins. Atomic resolution refinements using these evolving protocols have been performed on two small proteins, rubredoxin from Desulfovibrio vulgaris and the protein G immunoglobulin-binding domain. Appropriate treatment of the solvent structure in a protein crystal and the benefit to be gained by using sharpened density maps during refinement were investigated.