Since the classic description by Fuller Albright in the 1940s, primary hyperparathyroidism has evolved from a disease with classic signs and symptoms to a disease in search of symptoms! Since that time, two major events have occurred. First, in the United States, United Kingdom, and in most European countries, there has been a steady rise in the apparent incidence of the disease. Second, there has been a dramatic shift in the pattern of presentation. A majority of patients with primary hyperparathyroidism in countries with multichannel screening panels are asymptomatic. Skeletal and renal complications are uncommon, and osteitis fibrosa is rare. In contrast, the clinical presentation of primary hyperparathyroidism has changed very little in other regions such as the East, the Middle East, and some parts of the southern hemisphere over the same period of observation. Accordingly, we assessed the influence of vitamin D and calcium nutrition on the disease expression and parathyroid tumor growth in patients with primary hyperparathyroidism from different parts of the world. Between 1945 and 1950, both the prevalence of osteitis fibrosa and parathyroid tumor weight declined dramatically in the United States, coinciding with fortification of milk with vitamin D. In contrast, osteitis fibrosa and parathyroid tumor weight changed very little in parts of the world where vitamin D depletion is endemic. Furthermore, for a comparable degree of vitamin D depletion, Asian Indians have significantly larger tumors compared with Americans (3.95 +/- 2.23 vs. 0.66 +/- 2.84 g; p < 0.001). Within the United States, blacks have larger tumors compared with whites (0.78 +/- 2.87 vs. 0.58 +/- 2.78 g; p < 0.01). However, the slopes of regression between serum 25-hydroxyvitamin D, the best index of vitamin D nutrition, and parathyroid tumor weight, the best available index of parathyroid growth, were not significantly different between Asian Indians, whites, and blacks. We conclude that vitamin D and calcium nutrition of the population affect both the clinical expression and parathyroid tumor growth in patients with primary hyperparathyroidism. It will be of interest to see if the pattern of presentation of primary hyperparathyroidism changes when better nutritional policies are implemented in developing countries.