Purpose: There is increasing evidence of a central role for the calcium ion in blood pressure regulation. By studying blood pressure control in disorders of calcium homeostasis, a better understanding of the role of the calcium ion and certain calcitrophic hormones in modulating arterial pressure in humans may be gained. Our goal was to examine levels of blood pressure in a group of patients with either type Ia or type Ib pseudohypoparathyroidism (PsHP), a disorder characterized by target organ resistance to parathyroid hormone. Patients and Methods: Forty-six patients with type I PsHP were recruited for the study (28 with type Ia and 18 with type Ib). Blood pressure was measured and the degree of obesity was assessed in all patients. Detailed measurements of hormones involved in blood pressure regulation were made in nine hypertensive patients with PsHP. Results: Elevated arterial pressure was present in 18 of the 46 patients with PsHP, which comprised 53 percent (18 of 34) of the adult subjects. Prevalence of hypertension was similar in PsHP type Ia (nine of 21) and type Ib (nine of 13; p not significant) and was not related to coexisting hypothyroidism or degree of hypocalcemia. However, hypertension in PsHP was strongly linked to severe obesity. Mean body weights of normotensive and hypertensive patients with PsHP were 64 ± 2.8 (SEM) kg (125 ± 6 percent ideal body weight) and 96 ± 4.7 kg (172 ± 10 percent ideal body weight), respectively. Compared with obese hypertensive non-PsHP persons, hypertensive subjects with PsHP had reduced basal and posture-stimulated renin activity (basal, 1.68 ± 0.36 [n = 9] versus 3.97 ± 0.61 ng/ml/hour [n = 9] [p <0.05]; upright posture, 2.11 ± 0.42 versus 7.13 ng/ml/hour [p <0.05]; and lower basal and posture-stimulated plasma norepinephrine levels (basal, 236 ± 52 versus 426 ± 37 pg/ml [p, <0.05]; upright posture, 424 ± 62 versus 707 ± 64 pg/ml [p <0.05]). Conclusion: Our data suggest that hypertension is common in PsHP types Ia and Ib. This newly identified form of endocrine hypertension is strongly linked to excessive body weight but is associated with alterations in the renin-aldosterone and sympathetic nervous systems that are distinct from those encountered in obesity-related hypertension in the general population. The pathophysiologic basis for hypertension in these two distinctly different forms of PsHP remains to be determined.