Recent evidence suggests that cimetidine given pre-operatively in primary hyperparathyroidism (1 degree HPT) might cause structural changes in parathyroid glands, while its suppressive effects on the disease are disputable. To determine these possible changes we studied 38 patients with 1 degree HPT who underwent parathyroidectomy. In 14 of these (group I) cimetidine was given pre-operatively (1000 mg orally daily for 4 weeks). The remaining 24 patients (group II) did not take any drug. Parathyroid function was estimated by nephrogenous cAMP (NcAMP) and serum immunoreactive parathyroid hormone (iPTH) measurements. Histological examination of the parathyroids was made by conventional techniques. In group I at the end of cimetidine treatment, the only change observed was a small but significant (p less than 0.05) decrease of plasma calcium (-0.77 mg/dl). Histologically, the glands of group I--compared with those of group II--showed the following findings: increased gland mass: mean increase 1050 mg (adenomas) and 700 mg (hyperplasias); central oedema in all the cases of group I only; increased (about 50 per cent) cellular size and intranuclear 'inclusions' in 10 out of 14 cases of group I only. It is concluded that treatment with cimetidine in 1 degree HPT is followed by histopathologic alterations leading to increased size of the diseased parathyroids.