Achievement of maximal vasodilatation of the coronary microcirculation is a prerequisite for the measurement of coronary flow reserve (CFR). The present study was designed to address the hypothesis that intracoronary adenosine yields more complete vasodilation of the coronary microcirculation when incremental doses are used, resulting in higher and more accurate coronary flow reserve measurements. Four hundred and fifty-seven patients were divided in two groups; group I (319 patients) comprised patients without angiographic evidence of significant coronary artery disease, while group II (138 patients) comprised patients with intermediate coronary stenoses (between 40% and 70% diameter stenosis). Coronary velocity reserve (CVR, a surrogate measurement for CFR) was measured during cardiac catheterization using a Doppler-tipped guidewire. Incremental doses of intracoronary adenosine (12 to 54 microg for the left coronary artery and 6 to 42 microg for the right coronary artery) were administered. There was a significant difference between the initial dose of adenosine and the subsequent incremental doses. Of a total of 479 observations, only 192 (40%) had the maximal CVR value at the first dose. Thirty-nine percent of the patients in group I and 27% in group II with an initial CVR value < 2.5 increased CVR to > or = 2.5 with incremental doses of adenosine. This study suggests that incremental doses of adenosine should be used to achieve maximal CVR for the assessment of the functional significance of coronary lesions. Cathet Cardiovasc Intervent 2001;54:34-40.