The surgeon's gross evaluation, the hematoxylin and eosin stain, which assesses extracellular fat, and a new intracellular fat stain, osmium carmine, were comparatively evaluated in 30 consecutive patients who underwent surgery for primary hyperparathyroidism. The surgeon's gross judgment of enlarged and normal parathyroid tissue resulted in the correct functional assessment in 98% and 97% of the glands, respectively. The surgeon's functional assessment was correct in seven of 10 parathyroid glands that were considered by gross examination to be slightly enlarged (50 to 80 mg). The osmium carmine intracellular fat stain provided a correct functional assessment in all 10 of these glands. The osmium carmine stain also appears to have a role in providing scientific quantitative data to limit operations in patients who have a parathyroid adenoma to removal of the adenoma and biopsy of a grossly normal gland that demonstrates normal intracellular fat. Only one side of the neck was explored in 11 patients who fulfilled these criteria. There has been no persistent or recurrent hypercalcemia in these patients.