Thiazide diuretics are widely accepted as the cornerstone of antihypertensive treatment programs. Hypokalemia is a commonly encountered metabolic consequence of chronic thiazide therapy. We treated 38 patients (22 low renin, 16 normal renin) with moderate diastolic hypertension with hydrochlorothiazide (HCTC) administered on a twice daily schedule. Initial dose was 50 mg and the dose was increased at monthly intervals to 100 mg, 150 mg and 200 mg daily until blood pressure normalized. The serum K during the control period was 4.5 +/- 0.2 mEq/l an on 50, 100, 150 and 200 mg HCTZ daily 3.9 +/- 0.3, 3.4 +/- 0.2, 2.9 +/- 0.2, and 2.4 +/- 0.3 mEq/l, respectively. Corresponding figures for whole body K were 4107 +/- 208, 3722 +/- 319, 3628 +/- 257, 3551 +/- 336, and 3269 +/- 380 mEq, respectively. In 13 patients we observed the effects of HCTZ therapy (100 mg daily) on the occurrence of PVC's during rest as well as during static and dynamic exercise. During rest we observed 0.6 +/- 0.08 PVC beats/min +/- SEM and during static and dynamic exercise 0.6 +/- 0.06 and 0.8 +/- 0.15, respectively. Corresponding figures during HCTZ therapy 100 mg daily were 1.4 +/- 0.1, 3.6 +/- 0.7 and 5.7 4/- 0.8, respectively. The occurrence of PVC's correlated significantly with the fall in serum K+ observed r = 0.72, p less than 0.001. In conclusion we found that thiazide diuretics cause hypokalemia and depletion of body potassium. The more profound hypokalemia, the greater the propensity for the occurrence of PVC's.