1. In endothelium-containing rings of rat aorta, precontracted by phenylephrine, addition of acetylcholine (Ach), resulted in a concentration-dependent relaxation through the release of endothelial dependent relaxing factors, including nitric oxide (IC50 = 8.41 mu M). 2. Pretreatment of the tissues with 20 mu M indomethacin, significantly decreased the relaxation. 3. Preincubation of the preparations in medium solution in which sodium has been partially replaced by 0.5 mM lithium, significantly reduced Ach-induced endothelial dependent relaxation (EDR). 4. Lithium (2 mM) in medium, significantly increased Ach-induced relaxation. 5. As is shown in this study, lithium has two opposite actions on EDR, with the hose of 0.5 mM inhibiting, while the dose of 2 mM potentiates EDR. Thus it seems that the action of lithium on EDR is mediated through two separate mechanisms.