The safety of single and repetitive (paired and quadruple) focal transcranial magnetic stimuli as possible inducers of epileptic discharges or clinically manifest seizures was investigated in 21 patients with intractable epilepsy during invasive presurgical monitoring. Subdural and/or intracerebral depth electrodes had been implanted in close proximity to the suspected epileptogenic zone, and the anticonvulsant medication had been reduced. Focal transcranial magnetic stimuli were applied by a Magstim QuadroPulse magnetic stimulator over the hand area of the motor cortex ipsilateral to the epileptogenic focus at intensities of 120% and 150% of motor threshold and additionally as close as possible to the suspected epileptogenic zone at 40-100% of maximal stimulator output. Stimulation did not induce any complex partial or secondary generalized tonic-clonic seizures. One patient with hippocampal sclerosis experienced an aura associated with rhythmic electroencephalographic discharges restricted to the ipsilateral intrahippocampal depth electrode after stimulation over his left temporal lobe. This patient, however, also had frequent spontaneously occurring auras with focal ictal discharges originating from this hippocampus. Interictal discharges were not influenced significantly by single or repetitive magnetic stimuli. In conclusion, from this study there is no evidence that single or serial focal transcranial magnetic stimuli activate epileptogenic foci. At least four high-frequency repetitive stimuli of high intensity may thus be applied with a low risk of seizure induction even in patients with low seizure threshold.