Our aim was to evaluate the response of radiation synovectomy (RS) with yttrium-90 silicate ((90)Y-S) treatment of synovitis in patients with knee osteoarthritis (OA) and to derive factors that influence this response. The RS treatment response was assessed prospectively in 74 painful OA knees of 74 patients during a period of 6 months follow up. The duration of the disease was 24 +/- 9 months. Forty-four of the 74 knees had pain during the night and 43/74 had abnormal flexibility. Knee joints were graded according to the Steinbrocker radiological system. RS was performed according to the European Association of Nuclear Medicine guidelines. RS response was assessed considering the pain improvement from baseline values in terms of a 100-point visual analogue scale (VAS), the improvement of knee flexibility and the pain remission during the night. RS response was classified as poor (VAS<25), fair (VAS>or=25-50), good (VAS >or=50-75) and excellent (VAS>or=75), with excellent and good results considered as success, while fair and poor as failure. Our results show that 6 months after RS treatment, the percentage of VAS from baseline values was 66.0% +/- 24.8% and found to be significantly related to patients' age (P=0.01), duration of the disease (P=0.04) and to radiographic grading of OA (P=0.001). Knees without or with mineral type OA radiographic changes (Steinbrocker's grades 0-I) responded better than those with more advanced changes (Steinbrocker's grade III-IV) in terms of VAS improvement (77.9% versus 53.8%) (P < 0.001). The overall success rate (VAS >or= 50) was 83.8%. Remission of pain during the night was achieved in 88.6% and knee flexibility was improved in 65.1%. RS side effects assessed for the whole follow-up period were minor and not significant. In conclusion, RS with a single injection of (90)Y-S in patients with knee OA seems to have a significant therapeutic effect after a six months follow-up period with no significant side effects. Six months after RS treatment, clinical improvement was inversely related to radiographic knee damage, patients" age and duration of the disease. RS also induced remission of OA pain during the night.