Lortalamine is a new non-tricyclic anti-depressant compound. Lortalamine antagonizes in a dose-related manner reserpine-induced ptosis and hypothermia, and is far more potent than imipramine in this regard. The compound potentiates yohimbine toxicity in mice and, in the anesthetized dog, diminishes the tyramine pressure response while increasing the response to norepinephrine. These results would indicate the capacity for lortalamine to act as a norepinephrine uptake inhibitor, and indeed, lortalamine is more potent than imipramine in inhibiting norepinephrine uptake by rat brain cortex slices. Lortalamine does not inhibit serotonin uptake by rat midbrain slices. Lortalamine has a high affinity and high selectivity for the norepinephrine transporter. Lortalamine treated dogs showed, progressively, bilateral mydriasis, conjunctivitis, epiphora, corneal oedema and corneal erosions.