The distribution of substance P-like (SPLI) and methionine-enkephalin- like (MELI) immunoreactivity in the thoracic, lumbar, and sacral human spinal cord was studied in sections stained by the indirect antibody peroxidase-antiperoxidase method. The laminar distributions of SPLI and MELI were somewhat similar. Immunoreactive axons and terminal-like processes were found in the marginal zone and substantia gelatinosa, although SPLI was heavier than MELI in Lissauer's tract and the marginal zone. Laterally, both SPLI and MELI extended along the entire dorsal horn border, including laminae IV and V. Isolated, fine fiber bundles also extended deep into the central regions of laminae IV and V. Heavy SPLI and MELI also were found in the intermediolateral column region (IML), while lesser amounts were observed in the intercalatus and intermediomedial (IMM) regions of lamina VII. In lamina IX, SPLI was moderate, and less MELI was found. The distribution of SPLI fibers and terminal-like profiles in the human spinal cord is similar to that in other mammals, whereas that of MELI suggests some differences, particularly in laminae I, II, and III. Many terminal-like structures were in close apposition to neurons in several laminae. Based upon correlations of the three-dimensional organization of both the labeled terminals and the dendritic trees of the cells, the types of neurons in apposition to SPLI and MELI could be tentatively identified. These may include (1) marginal cells resembling the pyramidal and multipolar types; (2) gelatinosal cells resembling islet and stalked cells; (3) spinothalamic cells in laminae I, V, VI, VII, and VIII; (4) autonomic neurons in the IML and IMM; and (5) motoneurons in lamina IX. In the sacral cord, neurons resembling dorsal band (lamina V) and lateral band (lamina VII) parasympathetic neurons also were outlined by SPLI and MELI, with more SPLI in the region of the lateral band neurons. Often, in many of the laminae, the same neuron was surrounded by both SPLI and MELI. The variety of possible neuronal types supplied by SPLI and MELI processes and the fairly wide distribution of these substances within the spinal cord suggest that they may be involved in a number of spinal functions.