BACKGROUND Contrast-enhanced color Doppler ultrasonography is a non-radiation-bearing tool that can be of value for assessment of inflammatory and vascular synovial changes in juvenile rheumatoid arthritis (JRA). OBJECTIVE To evaluate the effect of contrast-enhanced color Doppler ultrasound (US) in the evaluation of synovial changes in the knees of children with JRA. METHODS Sagittal color Doppler sonograms of 31 knees in 22 patients with JRA and of 10 knees in 5 control subjects were obtained before (at baseline) and after (at peak contrast phase) intravenous injection of SHU 508. Images were assessed for overall mean pixel intensity within the synovial tissue and for peak enhancement ratios [[(mean pixel intensity values at maximum contrast enhancement-unenhanced mean pixel intensity values)/unenhanced mean pixel intensity values] x 100]. The joints were classified into three groups by clinical/laboratory criteria: group A (active disease in the knee), n = 9; group B (quiescent disease with serum chemistry levels of active disease), n = 12 and group C (remission disease), n = 10. RESULTS Mean color pixel intensity values were markedly increased by the use of US contrast agents in groups A (P = 0.004) and B (P = 0.0001), did not reach statistical significance in group C (P = 0.06) and remained essentially unchanged in the control group (P = 0.25). Enhancement ratios for the three groups of JRA patients were not different (P = 0.38) (mean +/- SD, 720% +/- 402 for group A, 731% +/- 703 for group B and 314% +/- 263 for group C). CONCLUSIONS Contrast-enhanced color Doppler imaging holds promise for the detection of active synovial inflammatory disease in subclinical cases of JRA, thereby allowing earlier treatment and improved clinical outcome.