A simple device for fluid exchange is described, which allows the exchange of an unlimited number of solutions at low (10-1000 nl/min) constant perfusion rate. The applicability of the system has been tested in microperfusion experiments of rat distal tubules. At a luminal perfusion rate of 40 nl/min, the lag time was some 20 sec and 80% fluid exchange time some 3 sec. Simple modification allows further reduction of the lag time. Under control conditions, the potential difference across the late distal tubule (PDte) approaches -19.4 +/- 2.5 mV (n = 27). Increase of luminal potassium concentration from 5.4 to 40 mmol/l hyperpolarizes PDte to -29.9 +/- 4.3 mV (n = 8). Amiloride (10 mumol/l) leads to a reversible depolarization to -3.2 +/- 1.0 mV (n = 19), barium (1 mmol/l) to a reversible hyperpolarization to -25.8 +/- 2.6 mV (n = 19). As expected, PDte is largely created by amiloride sensitive sodium channels and is partially blunted by barium sensitive potassium channels.