In a previous paper a markedly decreased activity of delta-aminolevulinate dehydratase (ALA-D) in patients with endemic nephropathy and in 24.6% of their healthy family members, was found. In this study the possible mechanisms of the decreased enzyme activity and the level of erythrocyte glutathione in patients and in healthy members from nephropathic families, were studied. We established decreased ALA-D activity in endemic nephropathy patients and in some healthy persons from their families. The normal concentration of erythrocyte glutathione was found in all groups. However, it was possible to reactivate the ALA-D enzyme in vitro by addition of exogenous glutathione. The obtained results suggested a normal synthesis of ALA-D apoenzyme and the existence of some factors whose effect upon enzyme activity was mediated through a binding to the reactive groups in the active centre of his enzyme or by oxidation of he reactive groups. Therefore, increased concentrations of sulfhydryl compounds, mostly of reduced glutathione are necessary for an optimal ALA-D activity.