AbstractIn the original study of the deleterious effects of oxidant drugs on persons heterozygous for nicotinamide adenine dinucleotide methemoglobin reductase (NADH MetHb R) deficiency, several Jewish physicians used as controls had decreased enzyme activity. We collected blood samples from 555 Jewish persons to 1) estimate the heterozygote frequency for NADH MetHb R deficiency; and 2) determine if external variables such as age, gender, and ingested medications may alter the NADH MetHb R activity and thereby alter estimates of heterozygosity. Two persons possibly heterozygous for the deficiency were identified (carrier incidence = 1/277; calculated homozygote incidence = 1/309,000 Jewish births). A difference in enzyme activity was found between males and females (P0.1) was seen between persons ingesting the following drugs and those not: Dilantin; antidepressants/sedatives; cardiac, antineoplastic, or antigout/antiinflammatory drugs; thyroid supplements, estrogen‐containing preparations, and antihistamines. NADH MetHb R activity did not correlate with age or spontaneous abortion. We conclude that heterozygosity for NADH MetHb R deficiency is not prevalent among Ashkenazic Jewish persons, and that external variables should be considered to ensure accurate interpretation of NADH MetHb R activity for correct estimation of heterozygosit