The aim of this study was to assess the impact of radiotherapy on serum vascular endothelial growth factor (VEGF) levels in patients with pharyngeal and laryngeal cancer. Serum VEGF concentrations were determined in 37 patients before, during, and after radiotherapy by using a quantitative sandwich enzyme immunoassay technique. Most (25 patients [68%]) of the studied population were found to have high pretreatment VEGF concentration (of >700 pg/mL; median, 796.3 pg/mL). During radiotherapy, after receiving the total dose of 40 Gy, the median level of serum VEGF remained unchanged (795.2 pg/mL). Regardless of the treatment results, 2 months after completing irradiation the median VEGF level decreased to 448.9 pg/mL, and the difference between pre- and posttreatment medians was statistically significant (P < .05). No association between pretreatment serum VEGF concentrations and the size of tumor, lymph node status, and patients' age was found. The findings that radiotherapy produces serum VEGF decline in primary pharyngeal and laryngeal carcinomas (P = .065) may be related to the blocking effect of radiation on local angiogenesis.