We determined the effect of local anesthetic and antiarrhythmic drugs which putatively increase cytosolic Ca2+ activity on fluid absorption (JV) by the isolated perfused proximal convoluted tubule of the rabbit. 2. Rabbit proximal convoluted tubules were perfused in vitro with an ultrafiltrate of modified Krebs-Henseleit solution containing 6.5 g/dl bovine albumin. 3. JV was measured before and after the addition of 2 mM tetracaine, 1 mM procaine or 5 microM verapamil, and after removal of the drugs from the bathing solution (recovery period). 4. All the drugs studied significantly inhibited JV in a reversible manner. 5. The data are consistent with the view that these drugs decreased the rate of fluid absorption in the proximal convoluted tubule by increasing cytosolic Ca2+ activity.