Accumulating evidence over the past decade indicates that synthetic retinoids may be capable of affecting both growth and differentiation of nervous tissue. Our aim was to substantiate possible side-effects of oral isotretinoin therapy on peripheral nerve functions, both neurologically and neurophysiologically. We performed neurological examination and electroneuromyographic studies on 18 patients with various skin diseases before, at the third month, and at the end of isotretinoin treatment. Abnormal neurophysiological findings in this study point towards a typical distal, length-dependent and predominantly sensory polyneuropathy. Clinicians should be aware of possible neurological sensorial symptoms during isotretinoin therapy. In our opinion, electroneuromyographic investigation should be performed on all patients reporting symptoms (e.g. paresthesia, numbness, sensory loss) before and during oral isotretinoin treatment. The precise clinical significance of the isotretinoin-induced neurophysiological alterations reported here remains to be determined in further studies.