The catecholaminergic cell groups in the human brain, denominated from A1 to A17, display some striking anatomical differences with those described in the rodent. These differences are essentially observed in the extent of the dopaminergic neurons and especially their axonal fields in the telencephalon. Immunocytochemistry for tyrosine-hydroxylase and dopamine-beta-hydroxylase allowed the visualization of the precocious human catecholaminergic groups as early as 4.5 postovulatory weeks. Maps of tyrosine-hydroxylase positive neurons generated in the different rhombomeres, midbrain, and prosomeres are shown following the prosomeric model introduced by Puelles and Rubenstein [(1993) Trends Neurosci. 16:472-476]. Such a description is convenient to compare catecholaminergic systems in different mammalian species and provide clear anatomical landmarks of the embryonic substantia nigra (midbrain and prosomeres 1 and 2), that are necessary for transplantation of neural tissue in Parkinson's disease. The development; and early specification of the dopaminergic neurons expressing calbindin D28K phenotype in the substantia nigra and in the ventral tegmental area are described. The catecholaminergic axons enter the anlage of the cerebral cortex just after the formation of the cortical plate, from 7 postovulatory weeks on. They invade the subplate layer where they wait for 4 weeks before penetrating the cortical plate. At midgestation, the different areas and layers of the frontal cerebral wall are invaded by the catecholaminergic axons, before the layering of the cortex is completed, in a pattern of fiber distribution similar to that described in the adult human brain. The early pattern of development of the catecholamine systems appeared to be phylogenetically well preserved in mammals, but specific features emerging during the differentiation period are unique to humans. Microsc. Res. Tech. 46:24-47, 1999. (C) 1999 Wiley-Liss, Inc.