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The effect of a short-term magnesium sulfate (MgSO4) infusion on venous plasma concen tration of noradrenaline (NA) and neuropeptide-Y-like immunoreactivity (NPY-LI) was investigated in 12 women with primary Raynaud's phenomenon (PRP) and in 12 healthy matched controls. The Raynaud's patients did not demonstrate any significant changes in mean basal plasma NA concentration (0.29 ±0.15 vs 0.37 ±0.09 ng/mL, ns) after MgSO4 infusion. However, in the controls there was more than twice the amount of circulating nora drenaline (cNA) (0.21 ±0.14 vs 0.54 ±0.22 ng/mL, P < 0.001) after MgSO4 infusion, compared with the preinfusion value. Measurements during the cold pressor test prior to the MgSO4 infusion showed a significant increase of cNA in both the PRP group and the control group (from 0.29 ±0.15 to 0.33 ±0.16 ng/mL, P < 0.05, and from 0.21 ±0.14 to 0.29 ±0.16 ng/mL, P < 0.005, respectively). After MgSO4 infusion the levels of cNA during the cold pressor test increased significantly only in the PRP group (from 0.37 ±0.09 to 0.41 ±0.11 ng/mL, P < 0.05). Circulating NPY-LI concentrations increased significantly during MgSO4 infusion in the Raynaud's patients as well as in the controls from 105 ±21 to 127 ±23 pmol/L, P4 infusion induced a sympathetic response, shown by the increased concentration of cNA and NPY-LI, while in PRP patients there was only an increase in NPY-LI. The discrepancy between PRP patients and healthy controls supports the view of a so-called "local fault" in the sympathetic nerve terminal of arterial/arteriolar walls in Raynaud's patients.