Villous cytotrophoblast cells display a range of morphological appearances that are assumed to reflect different stages of differentiation. Here we demonstrate that apoptosis and primary necrosis can also occur in these cells during normal early pregnancy, and should be included in the list of possible phenotypes. Samples from 30 placentae of 6-15 weeks gestational age were examined. Cytotrophoblast cells displaying highly condensed chromatin, but no karyorhexis, were observed detached from the basement membrane, and represented 0.49% (s.d.+/-0.36) of the total population. Their cytoplasm was heavily vacuolated, and their mitochondria swollen, indicating secondary necrosis. By contrast, extremely pale-staining cells with large rounded nuclei (volume-weighted mean volume 471.6 microm(3) compared to 250.1 microm(3) for euchromatic cells) were frequently observed (5.97% of total, s.d.+/-4.31). These cells displayed loss of euchromatin, a paucity of cytoplasmic organelles, and swelling of the mitochondrial intracristal space and endoplasmic reticulum. Nuclei of these cells displayed a significantly higher level of gold labelling using the TUNEL technique compared to euchromatic nuclei [1.0 particles/microm(2) (s.d.+/-0.13) vs 0.12 particles/microm(2) (s.d.+/-0.03),P< 0.05], confirming increased DNA fragmentation. We conclude that these cells are undergoing primary necrosis. The stimulus for both forms of cell death remains unknown, but may be associated with syncytiotrophoblastic stress.