A single injection of 100 micrograms reserpine into the crop of the medicinal leech, Hirudo medicinalis, reduced CNS serotonin and dopamine levels to less than 1% of control values within 3 d. High-pressure liquid chromotography- (HPLC) determined CNS serotonin and dopamine levels remained maximally depressed for approximately 1 month following reserpine injection. Subsequently, amine levels recovered slowly, but remained depressed 6 months after reserpine injection. Following reserpine treatment, glyoxylic acid-induced fluorescence or neutral red staining closely mirrored the HPLC-determined time course of amine depletion and recovery. Acute exposure of isolated ganglia to 10 microM reserpine for periods up to 6 hr produced a 20–30% reduction of serotonin and dopamine content. The threshold concentration of reserpine necessary to produce amine depletion was approximately 1 microM. We found that reserpine treatment eliminated biting behavior within 4 d following injection. Biting behavior remained depressed below control levels for approximately 4 months, but returned to control values while CNS serotonin and dopamine levels remained significantly depressed at this time. Unexpectedly, reserpine treatment increased rather than reduced the duration of stimulus-evoked swimming activity. This behavioral change was evident within 3 d and persisted for approximately 3.5 months. To rapidly restore amine levels in reserpine-treated animals, we bathed intact leeches in pond water containing serotonin, dopamine, or octopamine. We found that biting behavior was restored following reserpine treatment by bathing intact leeches in pond water containing serotonin or dopamine, but not octopamine. Also contrary to expectations, the increase in swim duration was not reversed by bath exposure to serotonin, dopamine, octopamine, or histamine. However, all swimming activity in reserpine- treated leeches was eliminated by the amine antagonist cyproheptadine. We propose that the presence of low levels of amines is critical for the expression of both biting and swimming activity in leeches. However, the minimal levels of amines necessary for the expression of these behaviors are lower for swimming than for biting.