The effects of Zinc and Mercury on human erythrocyte Acetylcholinesterase activity were studied. Blood used in this study was obtained from 24 apparently healthy individuals and after hemolysation, was treated with 3 different concentrations of Zinc and Mercury. Significant suppressions in Acetylcholinesterase activity were recorded in treated samples by Zinc and Mercury. When compared to controls the remaining activity was found to be 53% with the highest concentration of Zinc (2.1 mg/dl, P<0.01), 72% with the middle (1.4 mg/dl, P<0.01 and 85% with the lowest one (0.7 mg/dl, P<0.01). In the case of mercury, the remaining activity was found to be 55% with the highest concentration (8.4 ng/g, P<0.01), 72% with the middle (5.6 ng/g, P<0.01) and 79% with the lowest one (2.8 ng/g, P<0.01). Mercury showed a good correlation between doses used and decreases in activity (R=0.98). Zinc also showed a linear correlation (R=0.99). The direct interaction of metal ions with Acetylcholinesterase is proposed as a mechanism for depressed enzyme activity. It is concluded that Zinc and Mercury contamination during Acetylcholinesterase measurement can be a source of error that must to taken into account.