To discuss regulatory guidelines excluding subjects with erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency from lead-exposed jobs in the light of epidemiology findings on the mortality of these subjects. Two mortality follow-up studies were conducted. The first comprised 1979 male subjects newly identified as G6PD-deficient during a 1981 screening of the G6PD polymorphism among the general population in Sardinia, Italy. The second comprised 1080 male workers employed in maintenance and production departments of a lead smelting plant, who were divided into two subcohorts by erythrocyte G6PD phenotype. As compared with the general male population, G6PD-deficient subjects had significantly fewer deaths than expected from ischemic heart disease (standardized mortality ratio (SMR) = 28; 95% CI 10-62), cerebrovascular diseases (SMR = 22; 95% CI 6-55), and liver cirrhosis (SMR = 12; 95% CI 0-66). Among lead smelters the standardized mortality rates from cardiovascular diseases and all cancers observed among the G6PD-deficient subcohort were lower than those seen among subjects with the wild-type G6PD. No death from disease of the blood and hematopoietic system was observed among G6PD-deficient subjects in these two follow-up studies. These studies did not provide evidence of hypersensitivity to lead hematotoxicity among G6PD-deficient individuals at exposure levels within the current standards. Provided that workplace exposure complies with current standards, the hypothetical benefit of excluding G6PD-deficient individuals from lead-exposed jobs should be weighted against the loss of personal abilities and the economic damage in a social environment with diffuse unemployment.