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Regression analysis was used to estimate and test for relationships between blood lead, serum folate, red blood cell folate, serum vitamin B12, serum homocysteine, and neurobehavioral test performance in adults, 20–59 years old, participating in the third National Health and Nutrition Examination Survey. The three neurobehavioral tests included in the survey were simple reaction time, symbol–digit substitution, and serial digit learning. Serum folate, red blood cell folate, and serum vitamin B12 decreased as the blood lead concentration increased. Serum homocysteine increased as the blood lead concentration increased. Serum homocysteine decreased as the serum folate and serum vitamin B12 concentrations increased. Neurobehavioral test performance was not related to the blood lead, serum folate, or serum vitamin B12 concentrations. In adults 20–39 years old, performance on the serial digit learning test improved as the serum homocysteine concentration increased. In adults 40–59 years old, neurobehavioral test performance was not related to the serum homocysteine concentration. Homocysteine may impair cognitive function by acting at N-methyl-d-aspartate receptors, and improve cognitive function by acting at N-methyl-d-aspartate or γ-aminobutyric acid receptors.