Systemic phentolamine administration has been suggested as a diagnostic tool for identifying patients with sympathetically maintained pain (SMP) (Raja et al. 1991). The dose of phentolamine to produce adequate blockade of peripheral alpha-adrenoceptor function has, however, not been previously determined. In this study, the effects of two different doses of phentolamine on peripheral sympathetic vasoconstrictor function were investigated. One-hundred and seventeen (117) patients with chronic extremity pain underwent 130 phentolamine diagnostic tests using two different doses of phentolamine (0.5 mg/kg over 20 min (n = 60) and 1 mg/kg over 10 min (n = 59)). Eleven (11) patients did not receive phentolamine during the test. Cutaneous temperature was measured in the distal extremity before and after administration of phentolamine. In a subset of patients, baseline blood flow and sympathetically mediated vasoconstrictor response (SMR) to deep inhalation were measured on glabrous skin using laser Doppler flowmetry. SMR was elicited with a 5-sec maximal inspiratory gasp. A dose-related increase in cutaneous temperature was observed. In addition, baseline blood flow increased and SMR was attenuated after both doses of phentolamine, but to a greater degree after the 1 mg/kg dose. However, SMR was not completely attenuated, even after administration of the higher phentolamine dose. These results indicate that a phentolamine dose of 1 mg/kg over 10 min more completely blocks alpha-adrenoceptor function than a dose of 0.5 mg/kg over 20 min. We therefore recommend that to ensure adequate alpha-adrenoceptor blockade the higher phentolamine dose be used in the phentolamine diagnostic test for SMP.