The distribution of cytokeratin-positive interstitial trophoblast cells in the endometrium of the macaque during placental development was examined. Such cells are moderately abundant only from the 15th through the 22th day of pregnancy, although there is considerable individual variation. During this period of gestation, interstitial trophoblast cells are distributed in the perivascular stroma immediately surrounding spiral arteries, including coils of arteries already invaded by endovascular trophoblast. The interstitial trophoblast cells are not seen to directly intrude into the smooth muscle of the spiral arteries. Very few interstitial trophoblast cells are present from days 12 through 14 of gestation when the arteries are first invaded by endovascular trophoblast. Even fewer interstitial trophoblast cells are seen after day 30 of gestation. The brief time in gestation when interstitial trophoblast cells are abundant coincides with a time when spiral arteries are undergoing rapid modification into patent uteroplacental arteries. It is suggested that during this period, the interstitial trophoblast cells may facilitate changes in shape of the spiral arteries by alterations of the perivascular connective tissue, perhaps through interactions with other cellular constituents rather than by directly modifying the arteries per se.