Sensitivity of voltage-activated calcium currents to flow-induced mechanical stress was examined in enriched populations of rat anterior pituitary somatotrophs. Voltage-activated calcium currents were recorded with the whole-cell configuration of the patch-clamp technique. Pituitary cells were exposed to flow (from pipettes) which was produced by a hydrostatic pressure of about 3 cmH2O. In 92% of the cells studied (n = 87 cells) flow reduced the amplitude of both low voltage-activated (LVA) and high voltage-activated (HVA) calcium currents. These effects of flow on calcium currents did not result from changes in either seal resistance or leak conductance of the cell and were dependent on the magnitude of flow. The effect of flow is selective. We found that LVA calcium currents were substantially more sensitive to flow than HVA calcium currents. Under constant flow conditions, LVA calcium currents were reduced by 57.6 +/- 29.6% (S.D.), whereas HVA currents (recorded from the same cells) were reduced by only 17.8 +/- 15.9% (S.D.). The effects of flow on calcium currents were associated with effects on their related calcium tail currents. Slowly deactivating calcium tail currents were reduced by 75.3 +/- 25.6% (S.D.), whereas rapidly deactivating calcium tail currents were reduced by 29.1 +/- 14.4% (S.D.). The effect of flow on calcium currents was not associated with any significant shift in the activation curves of the calcium currents (voltage range -60 to +30 mV), suggesting that the effect of flow is not voltage dependent. The effect of flow is not dependent on activation of calcium currents during the exposure to flow. Calcium currents which were evoked immediately after cessation of the exposure to flow were reduced in amplitude and recovered to control values. Possible mechanisms underlying the flow effect and possible physiological relevance of the effect on pituitary cells are discussed.