Biochemical studies have shown that prohormone convertases PC1, PC2 and PC5A all have the capacity to process, with different specificities, the neurotensin/neuromedin N precursor, pro-NT/NN. A previous study from our laboratory has demonstrated that in rat brain, both PC2 and PC5A may be co-expressed with NT, lending support to a physiological implication of these two enzymes in the endoproteolytic maturation of pro-NT/NN. In the present study, we sought to determine whether PC1 might also be involved in this process by comparing the immunohistochemical distribution of the enzyme with that of NT in both singly labeled and dually labeled serial brain sections. PC1 was found to co-localize extensively with NT throughout the rat neuraxis. However, there were important regional variations in the proportion of NT neurons co-expressing PC1. Furthermore, this proportion was negatively correlated with that of NT neurons expressing PC5, suggesting that PC1 may serve as an alternative to PC5A for processing pro-NT/NN in mammalian brain.