Membrane depolarization is an early event in cell stimulation. Since the resting membrane potential is dependent on the potassium composition of the extracellular medium, we investigated whether there are clinical situations in which potassium levels are high enough to depolarize polymorphonuclear leukocytes. We determined the ionic composition of sterile and infected interstitial fluid in humans and guinea pigs. All sterile extravascular fluids had physiological potassium levels in the same range as serum values. In contrast, human abscess fluids contained increased K+-levels (17 +/- 6.4 mmol/liter, N = 8) and 15 of 20 experimental abscesses in guinea pigs contained greater than 10 mmol/liter K+. In humans three of eight abscess fluid K+ levels and in guinea pigs three of five abscess fluid K+ levels were even greater than 15 mmol/liter. Thus, high K+ levels, previously shown to activate polymorphonuclear leukocytes, are observed in certain clinical situations associated with local inflammation.