We have examined the physiological and morphological characteristics of spinal dorsal horn lamina I neurons with projections to the midbrain in the cat by combining physiological recording of neurons with the intracellular injection of HRP. Lamina I spinomesencephalic neurons were antidromically activated from the region that included the cuneiform nucleus and lateral periaqueductal gray at the intercollicular level. The majority of mesencephalic projection neurons (50 of 55) responded exclusively to noxious stimulation (nociceptive-specific) of their peripheral receptive fields. Lamina I spinomesencephalic neurons were activated from both the ipsilateral and contralateral midbrain and had slow antidromic conduction velocities (1 to 18 m/second). We identified eight cells with projections to both the midbrain and the thalamus and eight cells that were antidromically activated only from the thalamus. Intracellular injection of HRP revealed that lamina I spinomesencephalic neurons were of diverse morphological types, but generally had extensive, rostrocaudally oriented, dendritic arbors confined to lamina I and the overlying white matter. Axons were observed on nine of the HRP-filled spinomesencephalic neurons; five of the axons issued collateral branches. The morphological characteristics of these neurons did not appear to correlate with functional categories (i.e., wide-dynamic-range- or nociceptive-specific-type neurons). The large number of nociceptive-specific neurons with projections to the midbrain and the interconnections of these midbrain sites with hypothalamic and limbic structures suggest that the lamina I spinomesencephalic pathway plays an important role in the autonomic and affective responses to pain.