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 microM). 2. Pretreatment of the tissues with 20 microM 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 of EDR, with the dose 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.