An antiserum against conjugated histamine was used to study the distribution of histaminergic neurons in the CNS of the lamprey Lampetra fluviatilis. Numerous histamine-immunoreactive cell bodies were detected in the dorsal and ventral hypothalamic nuclei and in the adjacent postinfundibular commissural nucleus. Histamine-immunoreactive fibers of high density were present in the ventral hypothalamus, and fibers could also be traced dorsally from the hypothalamus to the corpus striatum and septal nucleus where they appeared to terminate in dense plexuses. Another, smaller group of histamine-immunoreactive perikarya was observed in the border area between mesencephalon and rhombencephalon, near the caudal pole of the mesencephalic reticular nucleus. Sparsely distributed histamine-immunoreactive fibers were present in the ventral mesencephalon. The distribution of histaminergic neurons in cyclostomes, which diverged very early from the main vertebrate line, shows similarities with the corresponding systems in the CNS of amphibians and mammals, which suggests that histaminergic neuronal systems are phylogenetically old and have been conserved during evolution.