To clarify the mechanisms of restenosis, restenotic human tissue specimens obtained by directional coronary atherectomy (DCA) in 43 patients were immunohistochemically analysed for cell proliferation and deposition of PG-Mlversican, an important extracellular matrix proteoglycan of the vessel wall. The patients were classified into five groups according to the period after percutaneous transluminal coronary angioplasty (PTCA): 0-1 month (N=6), 1-3 months (N=12), 3-6 months (N=ll), more than 6 months (N=6) and de n o w lesions (N=8). The tissue specimens were of 35 restenotic lesions following PTCA and eight primary stenotic lesions with no prior PTCA. Total cell numbers in the atherectomy specimens increased significantly up to 3 months after PTCA. Most cells were alpha-smooth muscle actin (a-SMA)-positive. To evaluate cell proliferation, the specimens were immunostained for Ki-67 antigen (clone MIB-1). A significant increase in the positive ratio was observed up to 1 month after PTCA, although the labelling index was less than 1 per cent at every stage. The deposition of PG-Mlversican, as analysed by imrnunohistochemistry, was greatest during the period 1-3 months after primary angioplasty, when restenosis detected by angiography progresses most actively. These results suggest that the peak of cell proliferation in the neointima occurs earlier than angiographic restenosis and that the deposition of PG-Mlversican may be a major factor in restenosis following angioplasty.