We have shown previously by electron microscopy that the purified glutathione S-transferase (GST)-Huntington'sdisease (HD) exon 1 fusion protein with 51 glutamine residues (GST-HD51) is an oligomer, and that site-specific proteolytic cleavage of this fusion protein results in the formation of insoluble more highly ordered protein aggregates with a fibrillar or ribbon-like morphology (E. Scherzinger et al. (1997) Cell 90, 549-558 ). Here we report that a truncated GST-HD exon 1 fusion protein with 51 glutamine residues, which lacks the proline-rich region C-terminal to the polyglutamine (polyQ) tract (GST-HD51ΔP) self-aggregates into high-molecular-mass protein aggregates without prior proteolytic cleavage. Electron micrographs of these protein aggregates revealed thread-like fibrils with a uniform diameter of ca. 25 nm. In contrast, proteolytic cleavage of GST-HD51ΔP resulted in the formation of numerous clusters of high-molecular-mass fibrils with a different, ribbon-like morphology. These structures were reminiscent of prion rods and Δ-amyloid fibrils in Alzheimer'sdisease. In agreement with our previous results with full-length GST-HD exon 1, the truncated fusion proteins GST-HD20ΔP and GST-HD30ΔP did not show any tendency to form more highly ordered structures, either with or without protease treatment.