Quantitation of coronary collateral flow in patients has been limited to angiographic techniques, which are subject to well-known methodologic limitations. The use of a Doppler-tipped angioplasty guidewire permits measurement of both antegrade and retrograde flow distal to totally or subtotally occluded vessels that may be supplied with acutely recruitable or angiographically mature collateral conduits. Using coronary flow velocity as an indicator of collateral flow, retrograde flow velocity was quantitated in 17 patients. Mean collateral flow velocity was approximately 30% of normal postangioplasty antegrade flow velocity. The phasic pattern of collateral flow was highly variable, but the retrograde diastolic and systolic flow velocity integrals were 20% and 40% (respectively) of post-procedure antegrade flow velocity. Preliminary studies with pharmacologic stimulation of the contralateral supply artery suggests that collateral flow is not increased by intracoronary nitroglycerin (200 micrograms) or adenosine (12 micrograms), but may be markedly augmented during mechanical stimulation of balloon occlusion. These data represent the first in a series of quantitative observations on control of the coronary collateral circulation in humans. Future investigations using the Doppler Flowire (Cardiometrics) will enhance understanding of factors modulating ischemia through collateral supply.