Hyperparathyroidism is caused mainly by three different conditions: namely, secondary hyperplasia, primary hyperplasia, and adenoma with only a few cases due to carcinomas. Histological distinction among these diseases is still difficult. In an attempt to characterize the three conditions, 17 cases from patients with hyperparathyroidism and 12 with normal glands were investigated immunohistochemically using antibodies against PTH, PTHrP, Ki-67 (MIB-1), and chromogranin A. The normal glands showed a diffuse staining pattern for PTH, and focal staining for PTHrP and for chromogranin A. Secondary hyperplasia demonstrated either focal, diffuse, or mixed staining in one gland with the three antibodies. For the primary hyperplasias and adenomas, the cases could be divided into two groups. The first group (group I), including 1 case of primary hyperplasia and 3 cases of adenoma, showed a homogeneous staining pattern with all three antibodies. A heterogeneous staining pattern similar to secondary hyperplasia was found in the other 8 cases that formed the second group (group II). There were five types of cytologic staining patterns after immunostaining. In secondary hyperplasia and group II, several patterns appeared simultaneously. On the contrary, only one pattern was found in group I. The proliferative index (P1) from Ki-67 staining of group I was also significantly higher than in group II. A lower P1 was observed in the normal glands. The present results indicate that different immunohistochemical characteristics exist in primary hyperplasias and in adenomas.