Indomethacin and oxamethacin reduce the formation of malonaldehyde from arachidonic acid by rat platelets in vitro. Sulindac has no influence on this formation. 2. Indomethacin, oxamethacin and sulindac inhibit the action of arachidonic acid on the rat stomach strips in vitro. 3. These three anti-inflammatory drugs suppress the hypotensive activity of arachidonic acid in the rat in vivo. 4. The comparison of the inhibitory activities of these drugs in vivo and in vitro shows that sulindac is converted to a potent anti-prostaglandin-synthetase metabolite and that a part of the action of oxamethacin depends on its conversion to indomethacin in the rat.