The proliferation of smooth muscle cells (SMCs) was suppressed in denudated rabbit aorta by holmium-yttrium-aluminum-garnet (Ho:YAG) laser intravascular irradiation. This study was dedicated to determine the applicability of the Ho:YAG laser irradiation on chronic restenosis after balloon angioplasty. The proliferation of SMCs in denudated rabbit aortas was suppressed in vivo 6 weeks after the laser irradiation of 20 pulses with 60 mJ per pulse. To investigate the mechanisms of this in vivo effect, the death of SMCs by the Ho:YAG laser-induced bubble collapse pressure was studied in vitro. No significant cell death attributed to this pressure was found. We conclude that the suppression of the proliferation of SMCs in vivo might not be caused by a reduction in density of SMCs induced by the collapse in pressure. We submit that the suppression of SMC proliferation in vivo could be caused by the bubble expansion pressure and/or heat induced by the laser irradiation.