Primary hyperparathyroidism was investigated using the presence of basic fibroblast growth factor (bFGF) from the immunohistochemical viewpoint with an anti-bFGF antibody in hyperplastic parathyroid glands of patients with multiple endocrine neoplasia type I (MEN-I) and of patients with non-MEN. The results corresponded well with the data from the DNA analysis. Twenty-five hyperplastic parathyroid glands from 11 patients with MEN-I and 38 glands from 20 patients with non-MEN primary hyperparathyroidism were stained immunohistochemically according to the avidin-biotin-peroxidase complex procedure. When 50% or more of the cells appeared uniformly stained, it was judged positively stained. In addition, 18 hyperplastic parathyroid glands from patients with MEN-I patients and 24 hyperplastic parathyroid glands from non-MEN patients were also analyzed for DNA using flow cytometry. The ratio of positively stained hyperplastic parathyroid glands was 72% in MEN-I patients and 18% in non-MEN patients. The difference between the two groups was significant (p < 0.01). The nodules consisted of oxyphilic cells in 7 of 25 hyperplastic parathyroid glands from MEN-I patients and in 10 of 38 hyperplastic parathyroid glands from non-MEN patients, and all the cells were positive for bFGF. There was no significant correlation between bFGF staining and the DNA ploidy pattern. bFGF possibly plays a role in the development of parathyroid gland hyperplasia, especially in MEN-I patients. The increase of oxyphilic cells may be correlated with the expression of bFGF.