This study examines immediate nitric oxide (NO) release from monocytes following interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) challenge in patients with complex regional pain syndrome (CRPS). Study patients exhibited the following: (1), mechanical allodynia; (2), evidence of either vasomotor or sudomotor disturbance; and (3), concordant painful allodynia documented with quantitative sensory testing that was temporarily abolished with sympathetic block. Ten subjects (CRPS, N = 5; control, N = 5) were enrolled. Peripheral blood monocytes were challenged with 100 mul of IL-1beta (1 ng), IFN-gamma (1 ng), TNF-alpha (0.01 ng), and normal saline (NS) and the resultant immediate NO release measured. Subjects with CRPS exhibited a statistically significant increase in NO release in response to IFN-gamma (P < 0.012) compared with controls. The NO responses to IFN-gamma in excess of NS (P < 0.025) and as the ratio IFN-gamma/NS (P < 0.022) were also significantly increased. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.