The fused thoraco-abdominal ganglia of the flies Calliphora vomitoria and Drosophila melanogaster were investigated immunocytochemically with antisera against histamine. In both insect species, 18 histaminelike immunoreactive (HA-IR) neurons were resolved in these ganglia. Six of these neurons have cell bodies in the thoracic neuromeres and 12 in the fused abdominal neuromeres. All cell bodies are situated ventrally. In Calliphora all cell bodies are arranged in a segmental pattern. In Drosophila only the thoracic cell bodies have a segmental arrangement, whereas the abdominal ones are clustered anteriorly close to the last thoracic neuromere. In both species the six thoracic neurons supply processes to the synaptic neuropil in the thoracic neuromeres and to the dorsal neural sheath. The processes in the neural sheath run anteriorly in the lateral portions of the ganglion into the cervical connective. In a few regions laterally arborizing terminals are found in putative neurohaemal areas. These areas were investigated by electron microscopic immunocytochemistry in Calliphora. The HA-IR terminals (containing small granular vesicles) were found outside the "blood-brain barrier" below the acellular basal lamina of the neural sheath. Release of histamine into the circulation is therefore theoretically possible. The central processes of the six thoracic HA-IR neurons may interact synaptically with large numbers of other neurons in the neuropil, and the peripheral varicose fibers from the same HA-IR neurons possibly are neurohaemal release sites. The abdominal HA-IR neurons, in contrast, form extensive arborizations within the synaptic neuropil only. Both thoracic and abdominal neurons have ipsilateral and contralateral branches as well as processes that invade more than one neuromere. A single HA-IR neuron thus invades large volumes of synaptic neuropil. Histamine may be used by neurons of the ventral ganglia both as neurotransmitter (or neuromodulator) and as a circulating neurohormone released from the neural sheath.