Presence of apoptotic cells and immunoreactivity to Ki-67, bcl-2 and p53 were studied in 20 cases of parathyroid adenoma. To determine apoptosis, the DNA nick end labeling method was used. 85% of the parathyroid adenomas were found to harbor apoptotic cells. All of the 20 adenomas contained Ki-67 immunoreactive cells. Proliferative activity was not more confined to nodular than to diffuse areas, but there was a highly significant difference in Ki-67 immunoreactivity between adenomatous tissue and the residual rim of normal tissue outside the adenoma. No Ki-67 immunoreactive cells were found in two normal parathyroid glands used as controls. All but one of the adenomas (95%) demonstrated immunoreactivity to bcl-2, but expression of p53 was detected in only a few adenomas (15%). There was a significant relationship between the adenoma weights and both Ki-67 and bcl-2. This study suggests that parathyroid adenomas contain cell populations with proliferative activity (clonal proliferation), but the weak immunoreactive expression of p53 combined with the relatively strong expression of bcl-2 might contribute to a slow glandular growth.