Microinjections of either 2 or 4 micrograms of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) were made into either the right or left frontal cortex of male rats pretreated with desmethylimipramine. Although both the 2 and 4 micrograms doses produced significant depletions of serotonin concentrations in the cortex and median raphe, neither dose produced a significant increase in spontaneous activity. This is in contrast to our findings with the noradrenergic neurotoxins, 6-hydroxydopamine and DSP-4, which produced hyperactivity following right but not left hemisphere injections. These findings do not rule out the involvement of 5-HT in the asymmetrically elicited hyperactivity but they do suggest some transmitter and neural pathway specificity to the lateralized response to cortical injury.