The inhibition of fluid absorption (Jv) by the antiarrhythmic and antihypertensive drugs propranolol and nifedipine, which increase cytosolic Ca2+ concentration, was studied using the isolated rabbit proximal convoluted tubule perfused in vitro. Proximal convoluted tubules were perfused and bathed with a modified Krebs-Henseleit solution containing bovine serum albumin. Jv was measured after a 30-min control period, after 40 min with either 0.1 mM propranolol or 1.0 mM nifedipine on the peritubular side and after a 40-min recovery period. Both drugs inhibited Jv (58% propranolol, and 21% nifedipine). The 40-min recovery period was sufficient to reverse the effect of nifedipine, but propranolol-treated tubules (N = 6) only reached 78% of the control Jv value. These results demonstrate that antiarrhythmic and antihypertensive drugs are powerful inhibitors of net fluid absorption by exerting a direct effect on proximal or distal tubule cells, thus acting like "local diuretics".