In 18 patients (12 women) presenting with effort-induced chest pain and normal coronary angiograms (syndrome X), 10 mg sublingual nifedipine increased the lumen of major coronary arteries (quantitative angiography) by 13 +/- 10% (p less than 0.01), coronary blood flow (thermodilution) by 23 +/- 26% (p less than 0.05), norepinephrine plasma concentration by 60 +/- 42% (p less than 0.01) and decreased the global ST-segment shift during the effort stress test from 8.8 +/- 4.1 to 7 +/- 6.8 mm (p less than 0.03) at comparable maximal workload and at unchanged double product. There was a correlation (positive) of changes in flow with changes in coronary lumen diameter (r = 0.65, p less than 0.01) with ST-segment response to exercise (r = 0.83, p less than 0.001) and with (inverse) norepinephrine plasma concentration (r = -0.70, p less than 0.01); no correlation was found between ST-segment response and changes in arterial lumen diameter. In a few cases, nifedipine did not improve or even worsened the response to exercise; coronary flow was unchanged or decreased and norepinephrine plasma levels were modestly or greatly increased, respectively. After 4 weeks of treatment with nifedipine (10 to 20 mg 4 times daily), the effort ST-segment shift was further decreased to 4.4 +/- 3.5 mm (p less than 0.03) despite a slightly increased double product. Plasma norepinephrine values, as compared to those after acute nifedipine, were decreased by 40% in patients with further improvement and were unchanged in patients whose exercise performance did not vary.(ABSTRACT TRUNCATED AT 250 WORDS)