Many types of chloride current have been reported in the hearts of various species; however, the nature of chloride conductance in the human heart is still unclear. We investigated cyclic AMP-dependent chloride current and swelling-induced chloride current in isolated human atrial cells using the whole-cell voltage-clamp method. External application of 1 microM isoprenaline increased calcium current by 391.9 +/- 48.6% (mean +/- S.D., n = 8); however, there was no activation of cyclic AMP-dependent chloride current at steady-state membrane potentials between -80 and +50 mV. Neither external application of 10 microM forskolin nor internal application of 50 microM cyclic AMP activated a cyclic AMP-dependent chloride current. On the other hand, when the same cell was superfused with a 50% hypotonic solution, it exhibited osmotic swelling and an outward rectifying current (6.59 +/- 0.96 pA/pF at +30 mV, n = 10). This swelling-induced current reversed at -26.5 +/- 3.1 mV (n = 10), close to the calculated equilibrium potential for chloride, and it was sensitive to the stilbene-derivative chloride channel blocker. In conclusion, no activation of cyclic AMP-dependent chloride current was observed in human atrial cells. On the other hand, a swelling-induced chloride current was consistently demonstrated and its kinetic properties were similar to those reported in other cardiac myocytes.