Octopamine and its precursor tyramine are biogenic amines that are found ubiquitously in insects, playing independent but opposite neuromodulatory roles in a wide spectrum of behaviors, ranging from locomotion and aggression to learning and memory. We used recently available antibodies to octopamine and tyramine to label the distribution of immunoreactive profiles in the brain and ventral nerve cord of the locust. In the brain and all ventral cord ganglia all known octopaminergic neurons were labeled with both the tyramine and octopamine antisera. In the brain the subesophageal ganglion and all fused abdominal ganglia we found somata that were only labeled by the tyramine antibody. Some prominent architectural features of the brain, like the protocerebral bridge, the central body, and associated neuropils, also contain intensely labeled tyramine-immunoreactive fibers. In addition, tyraminergic fibers occur in all ganglia of the ventral cord. For known octopaminergic neurons of the thoracic ganglia, octopamine-immunoreactivity was confined to the cell body and to the varicosities or boutons, whereas fiber processes always expressed tyramine-immunoreactivity. The distribution of the tyramine and octopamine content within these neurons turned out to be dependent on how the animal was handled before fixation for immunocytochemistry. We conclude that tyramine is an independent transmitter in locusts, and that in octopaminergic neurons the ratio between octopamine and its precursor tyramine is highly dynamic. J. Comp. Neurol. 512:433–452, 2009. © 2008 Wiley-Liss, Inc.