Our group has demonstrated that tangential radiation therapy (RT) to the left breast or chest wall can cause perfusion changes in the anterior myocardium. We assess if RT-induced perfusion changes are associated with the development of symptoms consistent with cardiac dysfunction. Between 1998 and 2001, 114 patients were enrolled into an institutional review board-approved prospective study and had pre-RT and serial post-RT (range, 6-24 months) single photon emission computed tomography (SPECT) scans to assess changes in regional cardiac perfusion. Thirty-one patients were excluded. The incidence of cardiac symptoms in patients with and without RT-induced perfusion defects was compared using a 2-tailed Fisher's exact test. With a median follow-up of 16 months (range, 6-24 months), 10 of 83 evaluable patients had > or = 1 episode of transient chest pain, occurring 0-14 months after RT (median, 6 months). The rates of chest pain in the patients with and without new perfusion defects were 9 of 31 and 1 of 52, respectively (P = 0.0004). A similar result was found when patients were segregated based on the use of chemotherapy. Two of these 10 cases were diagnosed as pericarditis. No patient had myocardial infarction or congestive heart failure. Cardiac symptoms occur more frequently in patients with perfusion abnormalities by SPECT after RT than in patients with normal SPECT scans, suggesting that such perfusion defects may be clinically significant. One confounding factor is that women who know they have RT-induced perfusion defects may be more likely to report episode of chest pain. Long-term follow-up will be necessary to better assess the clinical significance of RT-induced perfusion defects.