Epidemiological findings from the city of Cali, Colombia, support the hypothesis that water supply and iodine intake are not the only dietary factors which influence the magnitude of the goitre endemia. Experiments were conducted in rats to determine whether casein has a counteracting effect on the goitrogenic and antithyroid activities of methimazole (MMI) and goitrogenic water extracts (GWE) from the endemic area of the Cauca Valley. Female albino rats (Charles River, DC strain) 100–110 g initial weight, receiving 12 μg of iodine daily, were divided into three groups and put on special diets: protein-free, 8% casein, or 60% casein, respectively. Each group (24 rats) was then divided into three subgroups. Subgroup one received goitrogen-free water and was used as a control. Subgroup two was administered MMI, 50 μg/day/rat. Subgroup three was given per animal a daily amount of GWE equivalent in antithyroid potency to 50 μg of MMI. At 77 days, the thyroid glands were studied for weight, 131I uptake, and 127I concentration. Animals on the protein-free diet showed significantly (P < 0.05 – < 0.01) larger thyroid glands per 100 g body weight and lower thyroidal 4 h 131I uptake and 127I-concentrations than rats on casein diets. These differences were significantly increased (P < 0.01) by the administration of MMI and GWE. All the effects were completely reversed by the 60 % casein diet showing no differences between control rats and those on MMI or GWE. Rats on 8 % casein showed intermediate values between those of animals on protein-free and 60% casein diets; differences were still present between the control as against the MMI or GWE groups. The results indicate that under these experimental conditions, a poor-protein diet impairs the thyroidal transport of iodine, decreases its concentration in the thyroid and is accompanied by an enlargement of the gland. Under these circumstances, the action of thiourea-like antithyroid agents is enhanced. The administration of protein reverses these alterations and decreases the action of such antithyroid agents. Whether the changes observed are due to a direct action of casein on the thyroid and/or to effects of malnutrition on the metabolism of antithyroid compounds remains to be determined.