The effect on K+ currents (IK) of the general anaesthetic propofol (PR) (2,6-diisopropylphenol) was tested in undifferentiated clonal pheochromocytoma (PC 12) cells using the patch-clamp technique in whole-cell and single-channel configurations. PR decreased macroscopic IK amplitudes in a concentration-dependent way from 50 microM to 1 mM. The blocking effect was unchanged by repetitive depolarizing pulses and it was independent of the holding potential. Whereas activation of IK in control conditions was fitted by sigmoidal plus exponential time courses, only the sigmoidal time course gave an adequate fit with PR in the bath. The above effects were reversible. PR concentrations below 140 microM decreased single-channel activity for K+ channels with unitary conductance of 22 pS, in the voltage range between -40 and 60 mV from a holding potential of -50 mV. In contrast, the anaesthetic had nearly no effect on the opening probability of a channel with conductance of 10 pS. The unitary current amplitudes were unaffected in both channel types. These results suggest that PR action on IK may depend on the different blocking mechanisms of the K+ channels.