PART I: Coronary flow reserve indicates functional stenosis severity, but may be altered by physiologic conditions unrelated to stenosis geometry. To assess the effects of changing physiologic conditions on coronary flow reserve, aortic pressure and heart rate-blood pressure (rate-pressure) product were altered by phenylephrine and nitroprusside in 11 dogs. There was a total of 366 measurements, 26 without and 340 with acute stenoses of the left circumflex artery by a calibrated stenoser, providing percent area stenosis with flow reserve measured by flow meter after the administration of intracoronary adenosine. Absolute coronary flow reserve (maximal flow/rest flow) with no stenosis was 5.9 +/- 1.5 (1 SD) at control study, 7.0 +/- 2.2 after phenylephrine and 4.6 +/- 2.0 after nitroprusside, ranging from 2.0 to 12.1 depending on aortic pressure and rate-pressure product. However, relative coronary flow reserve (maximal flow with stenosis/normal maximal flow without stenosis) was independent of aortic pressure and rate-pressure product. Over the range of aortic pressures and rate-pressure products, the size of 1 SD expressed as a percent of mean absolute coronary flow reserve was +/- 43% without stenosis, and for each category of stenosis severity from 0 to 100% narrowing, it averaged +/- 45% compared with +/- 17% for relative coronary flow reserve. For example, for a 65% stenosis, absolute flow reserve was 5.2 +/- 1.7 (+/- 33% variation), whereas relative flow reserve was 0.9 +/- 0.09 (+/- 10% variation), where 1.0 is normal. Therefore, absolute coronary flow reserve by flow meter was highly variable for fixed stenoses depending on aortic pressure and rate-pressure product, whereas relative flow reserve more accurately and specifically described stenosis severity independent of physiologic conditions. Together, absolute and relative coronary flow reserve provide a more complete description of physiologic stenosis severity than either does alone. PART II: Coronary flow reserve directly measured by a flow meter is altered not only by stenosis, but also by physiologic variables. Stenosis flow reserve is derived from length, percent stenosis, absolute diameters and shape by quantitative coronary arteriography using standardized physiologic conditions. To study the relative merits of absolute coronary flow reserve measured by flow meter and stenosis flow reserve determined by quantitative coronary arteriography for assessing stenosis severity, aortic pressure and rate-pressure product were altered by phenylephrine and nitroprusside in 11 dogs, with 366 stenoses of the left circumflex artery by a calibrated stenoser providing percent area stenosis as described in Part I.(ABSTRACT TRUNCATED AT 400 WORDS)