We have used immunocytochemical methods to localize the homeodomain LIM protein Isl-l in the adult rat. M-1 immunoreactivity is expressed in polypeptide hormoneproducing cells of the endocrine system, in neurons of the peripheral nervous system, and in a subset of brain nuclei. Isl-l is also expressed in a subset of motoneurons in the spinal cord and brain stem, but not in regions of the central nervous system involved in sensory function or in neocortical areas. The pattern of expression of Isl-l suggests that this gene may be involved in the specification and maintenance of differentiated phenotypical properties of these cells.