Purpose: Evidence suggests that both humoral and cellular autoimmune processes directed toward heat shock proteins (hsp) contribute to the pathogenesis of atherosclerosis. We characterized a human hsp distinct from those previously characterized in atherosclerotic lesions, termed HDJ-2. Methods: To determine the role of HDJ-2 in atherosclerosis, we compared the level of HDJ-2 mRNA expression with the level of hsp60 and hsp70 mRNA expression in 26 carotid endarterectomy specimens and 17 normal arteries. The level of expression of HDJ-2 mRNA was also correlated to the presence of plaque ulceration and the degree of luminal stenosis associated with the lesion. Results: The expression of HDJ-2 and hsp70 was significantly higher in carotid artery plaques as compared with normal arteries: HDJ-2, 6.7 ± 1.6 vs 0.1 ± 0.04, (P = .001); hsp70, 9.5 ± 0.9 vs 3.7 ± 0.8, (P = .002). There was no significant difference in hsp60 expression between carotid artery plaques and normal arteries (21.0 ± 0.9 vs 20.6 ± 0.8, P = .65). Increased HDJ-2 expression in carotid artery plaques was independent of hsp70 (Pearson correlation, r = 0.11; Bartlett χ2 analysis, P = .71). Within the ulcerated plaque group, there was a correlation between degree of stenosis and high HDJ-2 mRNA expression (r = 0.896, P = .016). However, there was no correlation between degree of stenosis and high HDJ-2 mRNA expression within the nonulcerated plaque group (r = 0.530, P = .076) or within the entire group of patients (r = 0.0085, P = .97). Conclusion: These results demonstrate that expression of HDJ-2 is significantly increased in atherosclerotic carotid artery plaques as compared with hsp60 and hsp70 and correlates with luminal stenosis in ulcerated atherosclerotic carotid artery plaques.