Two patients with urticaria evoked at the site of contact of skin with water have been studied. Protection of the skin from contact with water by prior application of petrolatum ointment prevented wealing, but removal of the stratum corneum enhanced wealing.

Organic solvents did not themselves evoke wealing, but they enhanced the reaction to subsequent challenge by water.

That the release of acetylcholine is an essential step in the pharmacogenesis of wealing in aquagenic urticaria is indicated by the suppressive effect of locally-applied scopolamine on water–evoked wealing.

Aquagenic urticaria is also associated with elevated blood histamine levels and degranulation of mast cells in the water–challenged skin.

The relationship of acetylcholine and histamine to each other and to contact of water with the skin remains uncertain.