Restenosis after balloon aortic valvuloplasty is common, occurring in as many as half or more of patients in the first year. To gain understanding of the mechanisms of restenosis we examined results of second dilatations and the histology of restenosed valves excised during valve replacement for restenosis. Eleven patients with calcific aortic stenosis underwent second valvuloplasty for restenosis. The mean age was 82 +/- 6 years. The interval between first and second dilatation was 14.7 +/- 8.5 months. First valvuloplasty resulted in an increase in valve area from 0.63 +/- 0.23 to 1.09 +/- 0.32 cm2 (P<0.01). The valve area found after symptoms recurred was 0.56 +/- 0.18 cm2, not significantly different from the prevalvuloplasty dimensions. Second dilatation resulted in a mean aortic valve area of .76 +/- 0.22 cm2 (p=0.011 vs results of first valvuloplasty). The change in valve area after first dilatation was 0.45 +/- 0.17 vs 0.20 +/- 0.13 cm2 after second dilatation (p<0.01). Multiple histologic sections from excised, restenosed valves from five additional patients showed zones of active capillary and cellular proliferation and fibrosis in crevices between calcific nodules in three cases. Associated foci of ossification were seen in two of these. Stenotic nonvalvuloplasty control valves (n=19) showed no ossifications. In conclusion, histologic changes in restenosed valves differ from those seen initially in calcific aortic stenosis, with granulation tissue, fibrosis, and ossification being present. These findings may help to explain the limited results of second dilatations for restenosis.