Background: The use of pressor drugs after microsurgical free tissue transfer remains controversial because of potential vasoconstrictor effects on the free flap. Noninvasive monitoring of free flaps with laser Doppler flowmetry may provide further information regarding the local regulation of blood flow in the flap tissues during pressor infusions. This study evaluated the effects of four commonly used pressor agents. Methods: Twenty four patients (25 data sets) undergoing head and neck cancer resection and free flap reconstruction were recruited. Epinephrine, norepinephrine, dopexamine, and dobutamine were infused in a random order at four infusion rates, after surgery, with free flap and control area (deltoid region) laser Doppler skin blood flow monitoring. Frequency analysis of the Doppler waveform was performed utilizing the time period immediately before the first drug infusion for each patient as baseline. Results: At baseline there was less power at the 0.002–0.6 Hz frequency in the flap compared with control tissue consistent with surgical denervation. At maximum epinephrine infusion rates, the control of blood flow moved toward (i.e., proportion of power increased in) the lower frequencies, as smooth muscle mediated (myogenic) control began to dominate blood flow, an effect most marked with norepinephrine. Dobutamine and dopexamine had little effect on control of blood flow. Conclusions: Denervation of free flap tissue is demonstrable using spectral analysis of laser Doppler blood flow signals. With norepinephrine the control of blood flow shifts toward low frequency vasomotion where blood flow depends mostly on average blood pressure, making it potentially the most suitable agent following free tissue transfer. © 2013 Wiley Periodicals, Inc. Microsurgery, 2013.