A retrospective study of 22 hypertensive patients who were treated with thiazide diuretics for 2 to 12 yr revealed that 36% developed transient, self-limited asymptomatic elevations of serum calcium which occurred at varying periods of therapy and returned to normal within 2 to 4 wk despite continued administration of thiazides. These episodes of hypercalcemia correlated positively with increases in total protein, albumin, and globulin. The same phenomenon of intermittent hypercalcemia occurred in a prospective study of 11 patients but not in control subjects. The mean serum total calcium of the prospectively studied hydrochlorothiazide-treated patients was found to be higher than the nonthiazide control group. This difference was due to increased protein-bound calcium. The total proteins, serum albumin, and serum beta globulins of the treated group were higher, probably due to depletion of extracellular fluid. The presence of slightly elevated serum calcium in a patient treated with thiazides appears to be a common phenomenon and, unless it is marked, should not necessarily be construed as indicating covert hyperparathyroidism.