Despite expectations that excimer laser ablation would result in a low incidence of coronary dissection, studies have documented a 15-20% incidence of dissection (including a 4-6% incidence of clinically significant dissection) during excimer interventions. This investigation sought to determine if pressure pulses produced by the exposure of fluid phase media (blood and contrast) to 308-nm excimer radiation might contribute to untoward outcomes. Pressure pulses generated in these media were quantitated to be > 100 atm. In vitro ablation of porcine aorta in the presence of blood or contrast resulted in tissue dissection, while ablation in pure crystalloid did not. Next, a "flush and bathe" technique designed to replace all blood and contrast with crystalloid was applied to a pilot population of 57 consecutive patients. There were no rhythm disturbances or laser-related clinically significant dissections in this group, and the clinical success rate was 95%. In summary, this report quantitates a potential etiology for excimer dissection and suggests that replacement of blood and contrast with crystalloid might improve procedural and clinical success rates.