The role of serotonin (5-HT) transmission in the production of changes in rats' activity levels induced by 0.15 and 1.50 mEq/kg LiCl was assessed by selectively depleting 5-HT brain levels with p-chloroamphetamine prior to chronic administration of LiCl for 21 days. While p-chloroamphetamine pretreatment decreased 5-HT levels by 56%, irrespective of the fact that the animals had been administered either saline, 0.15, or 1.50 mEq/kg LiCl for 21 days, it did not alter the effects that each LiCl dose alone that on activity levels. Both LiCl administrations produced an 18% increase in 5-HT levels in rats pretreated with saline, yet diametrically opposed effects on activity levels. A parallel is drawn between these biochemical findings and previously reported data indicating that both LiCl doses produce an improvement in selective attention, yet opposed effects on rats' activity levels. The hypothesis that 5-HT transmission might be crucially involved in mediating the dose-independent effect of lithium on selective attention is proposed for future research.