A previous study found that potassium depletion in dogs that resulted in a reduction in plasma potassium from 4.1 to 3.2 mmol/L was associated with impairment of many aspects of left ventricular mechanical function, including a 51% reduction in the peak rate of left ventricular filling. To determine if potassium depletion had similar effects in humans, cardiac function was assessed by Doppler and two-dimensional echocardiography in 10 normal volunteers following a 7-day period of potassium depletion, and again 7 days of potassium repletion. Potassium concentration for the group averaged 3.49 +/- 0.12 mmol/L after the depletion period, and 4.57 +/- 0.14 mmol/L after repletion. Early peak mitral flow velocity was significantly less during depletion than during repletion. The values at rest were 89.5 +/- 6.6 and 77.0 +/- 4.9 cm/s during repletion and depletion, respectively (P < .01). Isovolomic relaxation time and deceleration time of flow through the mitral valve were also significantly increased during potassium depletion. No other measured indices of cardiac function were affected by potassium depletion. The results suggest that in normal volunteers, moderate potassium depletion may impair active relaxation of the left ventricle to a degree that is clinically significant.