This pilot study was undertaken to generate preliminary data on the accuracy of captopril-enhanced renal scintigraphy with a relatively new radiopharmaceutical, 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3) for detecting significant renal artery stenosis. Truth data was based either on arteriographic or outcome criteria (blood pressure response to therapy). Twenty-seven subjects with suspected renovascular hypertension were studied with baseline and captopril-enhanced 99Tcm-MAG3 renal scintigraphy and renal arteriography. Scan interpretations were expressed as a probability of a significant renal artery stenosis. Scan interpretations were compared with renal arteriographic results, renal vein renin levels, blood pressure values after renal artery repair, and blood pressure control after 4-26 months of clinical follow-up. Using > or = 50% luminal obstruction on arteriography as the reference standard for renal artery stenosis and a high probability scan representing a positive test, the test sensitivity and specificity were 33 and 97%, respectively (using high or indeterminate probability to represent a positive scan, the test sensitivity and specificity were 67 and 83%, respectively). The negative predictive value of a low probability scan for renal artery stenosis was 80%. However, including a measure of renovascular hypertension (blood pressure response to renal artery repair) as the reference standard, the accuracy of the scan improves, with the negative predictive value of a low probability scan for renovascular hypertension increasing to 97%. Scintigraphic results were also positively correlated with renal vein renin values in a statistically significant fashion (two-tailed Fisher exact test statistic = 6.43, P = 0.0219). Captopril-enhanced 99Tcm-MAG3 renal scintigraphy is a moderately accurate technique for detecting renal artery stenosis. More importantly, our preliminary findings suggest that the scintigraphic technique using 99Tcm-MAG3 appears to predict the blood pressure response to renal artery repair in subjects with suspected renovascular hypertension, thereby separating subjects with haemodynamically insignificant renal artery stenosis from those with renovascular hypertension.