This study examined the effect of alcohol(AL) on TSH and thyroid hormone, and the protective effect of selenium(SE) against alcohol-induced thyroid toxicity in guinea pigs. TSH values, thyroid hormones and enzyme activities were measured in serum from alcohol(15% v/v) and combination of sodium selenite(4ppm, AL+SE) with these drugs in drinking water-fed guinea pigs for 4 weeks. The morphological changes of thyroid gland were studied on paraffin-embedded sections stained with H-E stain. Body weight losses, high serum concentration in TSH, and low values in triiodothyronine(T₃), thyroxine(T₄), free T₄ and alkaline phosphatase(ALP) as well as high values in cholesterol were produced in a groups fed AL. In AL-fed group, the ratio of thyroid weight to body weight(ratio Twt/Bwt) was increased compared with controls, whereas the ratio Twt/Bwt was decreased in SE-fed group. However, the serum TSH, T₃, T₄, free T₄ and cholesterol values, and the ratio Twt/Bwt were reversed in groups given the combination of SE, compared with AL-fed group, also ALP values were reversed in groups given the combination of SE, compared with AL-fed group. In microscope, the thyroidal epithelia in AL-fed guinea-pig changed in squamous epithelium compared with control group and the nucleus of some thyroid cells were pyknosis. In AL+SE-fed guinea-pig, follicular colloid is high density in thyroid follicle and increased in connective tissue around the thyroid cells. The thyroidal epithelia were consist of cuboidal or columnar epithelium. This indicated that the morphological changes of thyroid are direct action in the thyroid cell. The results of this study confirmed that the toxic effect of AL on thyroid occur independently of changes in liver function, and that SE confers marked protection against AL-induced thyroid toxicity.