Exposure to nitrous oxide produces handling induced convulsions following withdrawal in mice. Since strain differences in responsiveness to the antinociceptive potency of N2O have been found, we examined whether there were differences in susceptibility to N2O withdrawal seizures. Significant differences were found between mouse strains, varying between 100% and 0% of mice exhibiting withdrawal seizures. There was a lack of correlation between the sensitivity of the mouse strains to N2O-induced analgesia and N2O withdrawal seizures, suggesting different mechanisms of action.