The mechanisms postulated to cause Raynaud's phenomenon include increased sympathetic nervous system activity, heightened digital vascular reactivity to vasoconstrictive stimuli, circulating vasoactive hormones, and decreased intravascular pressure.

The sympathetic nervous system mediates the digital vasoconstrictive response to cold exposure and emotional stress but has been discounted as a primary mechanism. Some investigators have suggested that increased sensitivity, increased numbers of postsynaptic alpha2-adrenergic receptors, or both enhance the vasoconstrictive reactivity to sympathetic stimulation.

In some cases of Raynaud's phenomenon, endogenous vasoactive substances (e.g., angiotensin II, serotonin, and thromboxane A2) and exogenous vasoconstrictors (e.g., ergot alkaloids and sympathomimetic drugs) may cause digital vasospasm. Many patients with Raynaud's phenomenon have hyperhidrosis (sweaty palms).