Studies were undertaken to explore the role of changes in serum calcium on blood pressure and the blood pressure response to antihypertensive drugs which block the renin-angiotensin axis. In 47 control experiments the baseline mean arterial pressure was 103.9 ± 1.29 mm Hg. After significant reduction of serum calcium in 26 experiments by thyroparathyroidectomy (TPTX; n = 18) or ethylenediaminetetraacetic acid (EDTA) infusion (n = 8) the mean arterial pressure was lower at 101.8 ± 2.94 mm Hg (p < 0.05). In 12 paired experiments TPTX reduced the mean arterial pressure from 107.8 ± 2.3 to8.5 9 ± 3.3 mm Hg (p < 0.01). In 10 experiments with different doses of EDTA infusion there was a linear correlation between serum calcium and mean arterial pressure (r = 0.91 p < 0.001). Plasma renin activity in normocalcemic animals was 1.52 ± 0.29 ng/ml/h and increased to 3.76 ± 0.85 ng/ml/h in hypocalcemic animals (p < 0.05). In 30 experiments in which angiotensin blockade was used in normocalcemic animals, the blood pressure decreased by -9.6 ± 1.8 mm Hg. in 22 hypocalcemic dogs the blood pressure decreased by –15.3 ± 1.93 mm Hg after angiotensin blockade with the same doses of the drugs (p < 0.05). In 5 paired experiments saralasin reduced blood pressure -2.2 ± 5.09 mm Hg (n. s.) under control normocalcemic conditions, but after being rendered hypocalcemic (TPTX) saralasin reduced blood pressure from 97.4 ± 7.02 to 83.6 ± 5.73 mm Hg (p < 0.01). Finally, there was a correlation between serum calcium and decrease in mean arterial pressure in response to saralasin (r = 0.766, p < 0.01) and in response to captopril (r = 0.6042, p < 0.05). In these investigations reduction of serum calcium decreased blood pressure, increased plasma renin activity, and potentiated the vasodepressor effects of saralasin and captopril. Elevations of calcium blunted the effects of