Patients with squamous cell carcinomas of the oral cavity are being increasingly treated by multimodal interdisciplinary regimes using a combination of surgery, chemo- and radiotherapy. Inflammatory alterations of the vascular endothelium following preoperative radiotherapy frequently cause healing delays of free flaps in the irradiated graft bed. The aim of the study was to investigate quantitative and qualitative changes of irradiated neck recipient vessels and transplant vessels used for microsurgical anastomoses in free flaps in patients undergoing preoperative radiotherapy or radiochemotherapy. In 348 patients (October 1995-March 2002) receiving primarly or secondary 356 microvascular hard- and soft tissue reconstruction, a total of 209 vessels were obtained from neck recipient vessels and transplant vessels during anastomosis. Three groups were analysed: group 1 (27 patients) treated with no radiotherapy or chemotherapy; group 2 (29 patients) treated with preoperative irradiation (40-50 Gy) and chemotherapy (800 mg/m2/day 5-FU and 20 mg/m2/day cisplatin) 1.5 months prior to surgery; group 3 (20 patients) treated with radiotherapy (60-70 Gy) (median interval 78.7 months; IQR: 31.3 months) prior to surgery. From each of the 209 vessel specimens, 3 sections were investigated histomorphometrically, qualitatively and quantitatively (ratio media area/total vessel area) by NIH-Image-digitized measurements. To evaluate these changes as a function of age, radiation dose and chemotherapy, a statistical analysis was performed using an analysis of covariance and chi 2 tests (p > 0.05, SPSS V10). In group 3, qualitative changes (intima dehiscence, hyalinosis) were found in recipient arteries significantly more frequently than in groups 1 and 2. For group 3 recipient arteries, histomorphometry revealed a significant decrease in the ratio media area/total vessel area (median 0.51, IQR 0.10) in comparison with groups 1 (p = 0.02) (median 0.61, IQR 0.29) and 2 (p = 0.046) (median 0.58, IQR 0.19). No significant difference was found between the vessels of groups 1 and 2 (p = 0.48). There were no significant differences in transplant arteries and recipient or transplant veins between the groups. Age and chemotherapy did not appear to have a significant influence on vessel changes in this study (p > 0.05). Following irradiation with 60-70 Gy, significant qualitative and quantitative histological changes to the recipient arteries, but not to the recipient veins, could be observed. In contrast, irradiation at a dose of 40-50 Gy and chemotherapy given at a median interval of 1.5 months prior to operation did not lead to significant histological changes to the recipient vessels.