This study investigated the effects of blind lithium discontinuation and resumption on measures of cognition, creativity, and fine motor performance in 46 lithium-maintained euthymic outpatients. Scores on memory measures, tests of tapping speed, and associative productivity all improved significantly during the time off of lithium. In an effort to further explain these results, analyses were undertaken with six possible intervening variables: age, sex, lithium concentration in plasma, thyroid function, duration of lithium maintenance, and depressive symptoms. Significant group and interactive effects are reported and discussed. A multiple regression analysis suggested that lithium has a greater neuropsychologic effect in younger, less-depressed patients having higher lithium concentrations in plasma.