The cause for the progressive vascular dilatation in port wine stains remains unclear. We compared the histology and ultrastructure of lesional and adjacent normal skin in paired biopsy specimens of 12 and 8 patients, respectively (age range, 6 to 53 years). In semithin sections, the lesions of all patients showed ectatic vessels and a fine-fibrous or hyaline thickening of the walls of postcapillary venules, as well as in some instances a loosening of the surrounding connective tissue. Ultrastructurally, the wall material consisted predominantly of peripheral deposits of amorphous material interspersed with collagen fibrils (diameter, 35 +/- 4 nm); occasionally the number of basal laminae in the inner part was also increased. Cross-banded filamentous aggregates with a periodicity of 95 nm were observed in and around the walls. The endothelium of many patients displayed fenestrations and/or small gaps. Various kinds of alterations of the intervascular connective tissue were found. We conclude that structural alterations of the vascular and later also of the intervascular connective tissue are related to the dilatation of the vessels. These findings are in agreement with the immunopathologically demonstrated increase of basement membrane components in the same biopsy specimens, but are interpreted as secondary phenomena. Endothelial stability and permeability may also be affected.