Nine neurodegenerative diseases, including Huntington's disease, are associated with the aggregation of proteins containing expanded polyglutamine sequences. The end result of polyglutamine aggregation is a β-sheet-rich deposit. There exists evidence that an important intermediate in the aggregation process involves intramolecular β-hairpin structures. However, little is known about the starting state, monomeric polyglutamine. Most experimental studies of monomeric polyglutamine have concluded that the backbone is completely disordered. However, such studies are hampered by the inherent tendency for polyglutamine to aggregate. A recent computational study suggested that the glutamine residues in polyglutamine tracts have a significant propensity to adopt the left-handed polyproline II (PII) helical conformation. In this work, we use NMR spectroscopy to demonstrate that glutamine residues possess a high propensity to adopt the PII conformation. We present circular dichroism spectra that indicate the presence of significant amounts of PII helical structure in short glutamine tracts. These data demonstrate that the propensity to adopt the PIIstructure is retained for glutamine repeats of up to at least 15 residues. Although other structures, such as α-helices and β-sheets, become possible at greater lengths, our data indicate that glutamine residues in monomeric polyglutamine have a significant propensity to adopt the PII structure, although not necessarily in long contiguous helical stretches. We note that we have no evidence to suggest that the observed PIIhelical structure is a precursor to polyglutamine aggregation. Nonetheless, increased understanding of monomeric polyglutamine structures will aid our understanding of the aggregation process.