During the development of the mammalian striatum, the early-forming dopamine innervation is broken up into macroscopic patches called "dopamine islands". These express high tyrosine hydroxylase-like immunoreactivity and are also rich in acetylcholinesterase activity. The mature striatum has prominent macroscopic compartments called "striosomes" that were first characterized by their low acetylcholinesterase activity and since have been related to heterogeneities in striatal input-output organizations. This report describes two sets of experiments designed to determine the relationship between the dopamine islands and the striosomes. The distributions of striatal tyrosine hydroxylase-like immunoreactivity and acetylcholinesterase activity were first compared in a series of kittens and young cats ranging in age from 1-228 postnatal days. During this time, the pattern of tyrosine hydroxylase-like immunoreactivity changed from islandic (patchy) to diffuse, and the pattern of acetylcholinesterase staining changed from one of acetylcholinesterase-rich patches to one of acetylcholinesterase-poor striosomes. The dopamine islands were in register with the acetylcholinesterase-poor patches at early developmental stages and at later stages the islands matched striosomes. These observations establish a correspondence between the dopamine islands and striosomes and demonstrate that the acetylcholinesterase-rich patches of the immature caudate nucleus become the acetylcholinesterase-poor striosomes of the adult. In a second set of experiments, cat fetuses were exposed to [3H]thymidine at embryonic days 22-29 in order to label the clustered subpopulations of striatal neurons known from previous experiments to lie in striosomes [Graybiel and Hickey (1982) Proc. natn. Acad. Sci. U.S.A. 79, 198-202]. The [3H]thymidine-labeled brains were examined at late fetal (embryonic days 50-52), early postnatal (days 1-21) and later postnatal (days 62-199) ages. The clusters of [3H]thymidine-labeled neurons were aligned with tyrosine hydroxylase-rich, acetylcholinesterase-rich patches early in development, and with acetylcholinesterase-poor striosomes at later stages. There were marked dorsoventral differences in the intensity of tyrosine hydroxylase-like immunoreactivity in the dopamine islands and this was confirmed in neonatal rats. A "dorsal islandic system" was defined as having crisp, highly immunoreactive islands; ventrally, regions of low and medium tyrosine hydroxylase-like immunoreactivity formed a mosaic.(ABSTRACT TRUNCATED AT 400 WORDS)