Effects of applied hydrostatic pressure on transmembrane potentials were investigated in sheep articular chondrocytes and human skin fibroblasts in non-confluent monolayer cultures. Resting potentials in chondrocytes (about -12 mv) and in fibroblasts (about -15 mV) were increased and decreased respectively by over 40% after pressure was applied cyclically (0.33 Hz, 120 mm Hg, 20 minutes). Continuous pressure (120 mm Hg, 20 minutes) caused deplorization in both cell types. Low frequency pressure application (less than 0.08 Hz) caused depolarization in chondrocytes and hyperpolarization in fibroblasts. Quinidine (2 x 10(-5) M) blocked and verapamil (10(-5) M) reduced hyperpolarization responses, suggesting involvement of Ca(2+)-dependent K+ channels. A23187 (1.9 x 10(-6) M) caused hyperpolarization in chondrocytes, augmented further by subsequent pressure application (0.33 Hz). Tetrodotoxin (10(-6) M) blocked depolarization responses indicating that these were due to Na+ influx. Blockade of histamine H1 receptors by chlorpheniramine maleate (5.1 x 10(-6) M), H2 receptors by cimetidine (7.9 x 10(-6) M) and beta-adrenoreceptors by sotolol (1.3 x 10(-4) M) had no effect on hydrostatic pressure-induced hyperpolarization in chondrocytes. Cytochalasin B (2 x 10(-5) M and at 4 x 10(-6) M) abolished pressure-induced hyperpolarization in chondrocytes; in contrast, applied cyclical hydrostatic pressure to cytochalasin-treated fibroblasts caused hyper-polarization, suggesting that cytoskeletal changes were involved.