Study objective: Although cellular proliferation is considered one of the dominant processes leading to restenosis following coronary intervention, controversy exists over the extent of cellular replication in atherosclerotic tissue. Accordingly, we sought to investigate the level and clinicopathologic correlates of proliferative activity in atherosclerotic tissue obtained via directional coronary atherectomy (DCA). Design: Prospective observational study. Setting: Tertiary care referral hospital. Patients: Specimens retrieved via DCA from 37 lesions (primary, 26; restenosis, 11) were studied using single-label immunohistochemical staining for the proliferating cell nuclear antigen and basic fibroblast growth factor (bFGF). Results: Restenosis tissue was significantly more likely than primary tissue to contain areas of intimal hyperplasia (64 vs 23%; p<0.03). However, the frequency of positive staining for proliferating cell nuclear antigen (PCNA) was similar in primary and restenosis lesions (25 vs 30%; p=NS), and the mean percentage of positive cells per slide was similar in the two groups. Positive immunostaining for bFGF was present in 20 lesions (61%), and tended to be more frequently seen in restenotic lesions (80 vs 52%; p=0.25). However, there was no correlation or colocalization between immunostaining for bFGF and proliferating cell nuclear antigen. We found no clinicopathologic correlations with respect to clinical outcome. Conclusion: Cellular replication, as measured by expression of the PCNA, occurs in a heterogeneous pattern in both primary and restenotic atherosclerotic tissue obtained from patients undergoing coronary intervention.