We studied the neurobehavioral effects of prenatal exposure of MT-null and wild-type mice to elemental mercury vapor (Hg0). Pregnant mice of both strains were repeatedly exposed to Hg0 vapor at 0.50 and 0.56 mg/m3 for 6 h/day until the 18th day of gestation. The behavioral effects were evaluated with locomotor activity in the open field, learning ability in the passive avoidance response and spatial learning ability in the Morris water maze at 12 weeks of age. Hg0-exposed MT-null mice showed a significant decrease in total locomotor activity in males, and a learning disability in the passive avoidance response and a retarded acquisition in the Morris water maze in females as compared with the control. In contrast, Hg0-exposed wild-type mice did not differ from controls in the three behavioral measurements. The results indicate that MT-null mice would be more susceptible than wild-type mice to the behavioral neurotoxicity of prenatal Hg0 exposure. Mercury concentrations in the brain of both strains were slightly higher in the exposed group than in the control group, indicating the retention of residual mercury even 12 weeks after the cessation of the exposure. Brain concentrations of mercury were also significantly higher in the exposed-females than exposed-males in either strain. From these results, we suggest that the increased susceptibility of MT-null females to behavioral changes caused by prenatal Hg0 exposure is due to a greater retention of mercury and lack of MT-I,-II in the brain.