The distribution of histamine-, octopamine-, gamma-aminobutyric acid- (GABA) and taurine-like immunoreactivity in the bivalve mollusc Macoma balthica was studied immunocytochemically with antisera produced in rabbits. Histamine levels in the ganglia and whole animals were also measured by high-performance liquid chromatography using a postcolumn derivatization method. Immunoreactivity for these substances, except for taurine, is found in the central nervous system of this species. The most extensive neuronal system is revealed with the antiserum against histamine. All the main ganglia contain histamine-immunoreactive cell bodies, and a dense network of nerve fibers is seen in the ganglia and nerve roots. Histamine-immunoreactive nerve fibers project to the mantle edge, lips and oesophagus. The basal part of the inhalant siphon is rich in histamine-immunoreactive fibers. Unlike histamine, octopamine- and GABA-like immunoreactivities are restricted to the central nervous system. Taurine-like immunoreactivity is not found in the nervous system of this species. In the nervous system, histamine-immunoreactive cell bodies and fibers are more numerous than those that are octopamine- and GABA-immunoreactive. The distribution of these substances in the ganglia is different. GABA-immunoreactive cells are typically smaller than most of the histamine- and octapamine-immunoreactive cells. Most GABA- and octopamine-immunoreactive cells and fibers are located in the pedal ganglion. Histamine is distributed more evenly in the ganglia and nerve roots. The biochemical measurements of histamine correlate well with the immunohistochemical findings and confirm the predominant location of the amine in the nervous tissue. These results suggest that histamine is more widespread than some other putative transmitters, and support the concept that histamine may have an important role in many physiological processes in molluscs.