The protective effect exerted by alpha-lipoic-acid (ALA) (62464) against the acute toxic action of arsenic (7440382) (As), gold (7440575) (Au), mercury (7439976) (Hg), and lead (7439921) (Pb) was investigated in Swiss-Webster-mice and beagle-dogs. In mice treated subcutaneously with a one hundred percent lethal dose of As, simultaneous intraperitoneal injection of ALA completely prevented mortality. ALA was also shown to reverse the toxic effect of As when given to mice that were already showing overt signs of As intoxication. Dimercaprol (59529) (BAL) and a higher homolog of ALA, 3-(6-carbohexyl)-1,2-dithiolane, proved to be as effective as ALA in protecting mice against As intoxication, while thiomalic-acid (70495) was ineffective in this respect. Tests carried out in dogs confirmed the effectiveness of ALA in the treatment of As induced acute toxicity. In mice treated with Hg, the simultaneous administration of ALA fully protected the animals against the lethal effects of the metal, although the number of molecular equivalents required to achieve protection was greater than for As. BAL was less effective than ALA in preventing Hg induced toxicity. ALA failed to demonstrate any protective effect against Pb induced acute toxicity. The simultaneous administration of two molar equivalents of ALA protected the animals from the toxic effects induced by Au in a dose of 100mg/kg, but no protection was seen when ALA was given 48 hours after Au. BAL was twice as effective as ALA against the acute toxic effects of Au.