2,3 Dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) are chelating agents that have been employed in the treatment of metal intoxication. Because the therapeutic mechanism underlying the action of these compounds involves promoting metal excretion from the body, potential interaction between clinically employed chelating agents and endogenous metals, for instance zinc, is probable. d-Aminolevulinate dehydratase (d-ALA-D) is a metalloenzyme requiring zinc ions for the activity. d-ALA-D is a sulfhydryl containing enzyme, which catalyses the asymmetric condensation of two molecules of d-aminolevulinic acid (d-ALA) to porphobilinogen in the initial steps of heme biosynthesis. In the present investigation, we examined the effect of cadmium (CdCl₂) on δ-ALA-D activity from rat lungs in vitro. Furthermore, a possible protective effect of dithiol chelating agents, DMSA and DMPS, was studied. d-ALA-D activity was assayed according to the method of Sassa (1982). Data were analyzed statistically by one-way ANOVA, followed by Duncan's Multiple Range Test when appropriate. The results demonstrated that CdCl₂ significantly inhibited δ-ALA-D activity, and calculated IC₅₀ was 35 μM. DMSA and DMPS, at different concentrations 1- 100 μM, did not restore the inhibitory effect of CdCl₂ (35 μM) on δ-ALA-D activity. DMPS in combination with CdCl₂ caused a more pronounced inhibition of δ-ALA-D activity (68, 71, 85 and 91%, respectively) when compared with CdCl₂ exposition alone. Accordingly, DMSA (100 μM) plus CdCl₂ demonstrated a higher reduction of enzyme activity when compared to metal alone (78% of inhibition). We can suggest that the chelating agents tested increased the inhibitory effect of CdCl₂ on δ-ALA-D activity in rat lungs in vitro.