The significance of apoptosis in human gastric carcinomas was investigated in comparison with proliferative activity and p53 accumulation, using an in situ DNA nick end labeling method and immunohistochemistry for both Ki-67 antigen and p53 protein. Apoptotic labeling indices (LI) of 51 differentiated carcinomas (21 of early and 22 of advanced stage) were significantly lower than for 33 undifferentiated tumors (9 of early and 24 of advanced stage) (P < 0.05). In both types, apoptotic LI of advanced stage lesions were significantly higher than for the early stage cases (P < 0.005, P < 0.03). The distribution of apoptotic cells was different from that of Ki-67-positive cells, generally exhibiting an inverse correlation for areas of predominance. In contrast, there was no significant correlation between p53 immunoreactivity and either apoptotic LI or Ki-67 LI. It is concluded that in human gastric carcinomas the susceptibility to apoptosis is related to tumor cell differentiation and depth of invasion, and may play a role in selection of clonal subpopulations with high growth potential.