Restenosis within tubular slotted stents is secondary to intimal hyperplasia and is usually treated with percutaneous transluminal coronary angioplasty (PTCA). Sequential intravascular ultrasound (IVUS) was used to assess the mechanisms and results of PTCA for in-stent restenosis. Sixty-four restenotic Palmaz-Schatz stents were studied by IVUS imaging before and after PTCA. IVUS measurements of stent and lumen cross-sectional areas (CSAs) at 5 segments (proximal and distal stent edges, proximal and distal stent bodies, and the central articulation) were used to calculate intimal hyperplasia CSA (stent-lumen CSA). The results of the 5 segments were then averaged. Mean and minimum CSAs were compared before and after PTCA. Quantitative angiographic measurements showed a minimal lumen diameter increase from 1.05 +/- 0.63 mm (mean +/- 1 SD) before intervention to 2.77 +/- 0.51 mm after PTCA (p < 0.0001). Conversely, the diameter stenosis decreased from 63 +/- 19% to 18 +/- 12% (p < 0.0001). IVUS measurements showed a minimum lumen CSA increase from 2.3 +/- 1.3 mm2 to 6.1 +/- 2.2 mm2 (p < 0.0001) as a result of an increased minimum stent CSA (7.2 +/- 2.4 mm2 to 8.7 +/- 2.6 mm2, p < 0.0001) and a decreased intimal hyperplasia CSA within the stent (4.9 +/- 2.2 mm2 to 2.7 +/- 2.0 mm2, p < 0.0001). Of the total mean lumen enlargement, 56 +/- 28% was the result of additional stent expansion and 44 +/- 28% was the result of a decrease in neointimal tissue. The minimum lumen CSA after PTCA was significantly smaller than the minimum stent CSA before PTCA (presumably an accurate reflection of lumen dimensions immediately after stent implantation; p = 0.0002). The mechanism of PTCA for restenosis is a combination of additional stent expansion and tissue extrusion out of the stent; there is a relatively high residual stenosis (angiographic diameter stenosis of 18 +/- 12%).