The distribution and the ontogeny of substance P (SP)-immunoreactive structures were investigated in the various cortical areas of macaque monkey cerebrum at embryonic day 120 (E120), embryonic day 140 (E140), newborn (Nb), postnatal day 30, postnatal day 60 (P60) and adult stages, using an immunohistochemical method. SP-immunoreactive cell bodies and fibers were detectable at E120 and the cell number increased until Nb stage. At E140, many immunoreactive cells were present in the upper part of layer V. Some of them seemed to be developing pyramidal cells which ascended their fibers toward layer I. After Nb stage, the number of immunoreactive structures decreased. By P60, the distribution patterns of SP-immunoreactive structures reached the adult level. Between Nb and P60, we occasionally observed structures which were presumably degenerated neurons and fibers. The distribution and developmental ontogeny of immunoreactivities were different among the various cortical areas. In areas OC and FA (von Bonin and Bailey), we observed the high densities of immunoreactive fibers and terminals, in spite of low numbers of cell somatas. While, in the association areas (areas FD, PE, TA and TE), there existed larger numbers of immunoreactive cells at E140 and newborn stages, following the decrease of cell number until P60. Our present study shows the transient increase and the following decrease of the numbers of SP-immunoreactive cells. Since we observed SP-immunoreactive pyramidal cells and degenerating cells during development, the decrease of immunoreactivities may be due to both cell death and change in phenotype.