The 577-nm flashlamp-pumped tunable dye laser pulsed at 450 microseconds is rapidly becoming the treatment of choice for removal of port-wine stains and other vascular ectasias. In this study, we examined the mechanisms of vessel destruction by determining the effects of laser irradiation on three types of primary target cells in vitro: erythrocytes, endothelial cells, and fibroblasts. Clinical studies were also performed, addressing the efficacy of this laser in the treatment of port-wine stains of the head and neck, trunk, and extremities. In endothelial cell cultures, both [3H]thymidine (measuring cell proliferation) and [3H]leucine (measuring protein synthesis) incorporations were inhibited at energy levels of 5-12 J/cm2 (p less than 0.01). The laser energy in the range of 5-8.5 J/cm2 had no effect on cell viability. Erythrocytes as target cells for laser energy demonstrated rapid, dose-dependent lysis. Addition of erythrocytes into a co-culture with endothelial cells abolished the direct inhibitory effect noted in cultures when endothelial cells alone were present. The results of the latter experiment imply that erythrocytes are the primary target cell absorbing the laser energy at 577 nm. However, direct laser effects on endothelial cells may also contribute to the mechanisms of ablation of the vascular ectasias by the tunable dye laser at 577 nm. Clinical trials on 28 patients with port-wine stains of the face and neck using this laser demonstrated a 75% response rate with greater than 50% lightening of the lesions. Of 9 port-wine stain lesions on the trunk and extremities (on a total of 6 patients), 8 (89%) demonstrated significant (greater than 50%) fading of their lesions. Complications such as scarring or epidermal texture changes were minimal.