BACKGROUND Incorporating kilohertz-frequency signals in transcutaneous electrical stimulation has been proposed as a means to overcome the impedance of the skin, thereby reaching deeper nerves. In particular, a transdermal amplitude modulated signal (TAMS), composed of a 210 kHz non-zero offset carrier modulated by rectangular pulses, was introduced recently for the treatment of overactive bladder. However, the contribution of the components of TAMS to nerve fiber activation has not been quantified. METHODS We conducted in vivo experiments and applied direct stimulation to the sciatic nerve of cats and rats. We measured electromyogram and compound action potential activity evoked by pulses, TAMS and modified versions of TAMS in which we varied the size of the carrier. RESULTS Nerve fiber activation using TAMS showed no difference with respect to activation with conventional pulse for carrier frequencies of 20 kHz and higher, regardless the relative amplitude of the carrier. For frequencies lower than 20 kHz, the offset needed to generate half of the maximal evoked response decreased significantly with respect to the pulse. Results of simulations in a computational model of nerve fiber stimulation using the same stimulation waveforms closely matched our experimental measurements. CONCLUSION Taken together, these results suggest that a TAMS with carrier frequencies textgreater20 kHz does not offer any advantage over conventional pulses, even with larger amplitudes of the carrier, and this has implications for design of waveforms for efficient and effective transcutaneous stimulation.