The inhibitory effect of various forms of organic selenium compounds and of diphenyl ditelluride (PhTe)₂on δ-aminolevulinate dehydratase (δ-ALA-D) from liver, kidney, and brain of rats was investigated because it has been reported that organocalcogens catalyze the oxidation of thiols. Diphenyl diselenide (PhSe)₂, ρ-chloro-diphenyl diselenide (ρClPhSe)₂, propyl-2-2-diphenyl diselenide, and propyl-2-methoxy-2-phenyl selenide inhibited δ-ALA-D and the IC50 ranged from 2 to 32 μM depending on the selenium compound and whether it was preincubated with the enzyme. (ρClPhSe)₂was the most potent inhibitor of δ-ALA-D, and preincubation increased the inhibitory potency of all the tested compounds. Inorganic selenium compounds (sodium selenite, Na₂SeO₃and selenium dioxide, SeO₂) inhibited δ-ALA-D, and the potency of SeO₂was greater than that of (ρClPhSe)₂. Diphenyl ditelluride (PhTe)₂also inhibited δ-ALA-D but with relatively lower potency than that of organic and inorganic selenium compounds. The inhibitory effect of propyl-2-2-diphenyl diselenide and propyl-2-methoxy-2-phenyl selenide seems to be mediated by (PhSe)₂since the compounds decomposed rapidly to (PhSe)₂in aqueous medium. The inhibitory action of selenium forms on δ-ALA-D from liver, kidney, and brain was antagonized by sulfhydryl protecting agents (dithiotreitol and reduced glutathione). The effects of organic selenium compounds on δ-ALA-D were related to the stability of the Se–Se (or Se–C) bond because the compound methyl-diphenyl diselenide (which possesses the most stable Se–C–Se bond) did not inhibit the enzyme. The inhibitory action of (PhSe)₂was not related to the formation of oxyradicals in the medium since superoxide dismutase and catalase did not affect the inhibition of δ-ALA-D by (PhSe)₂. δ-ALA-D from cucumber leaves was not inhibited by selenium or tellurium compounds, which suggests that these compounds act directly on the B or β-site of the animal enzyme. These results suggest that δ-ALA-D from liver, kidney, and brain is a potential molecular target for the toxic effect of organic forms of selenium and tellurium.