The SK3 channel, a small-conductance calcium-activated potassium channel, is expressed in immature fibers of skeletal muscle and becomes down regulated after innervation. We have previously shown that the level of mRNA of the SK3 channel is increased in muscle from myotonic dystrophy. In this study, we have carried out an immunohistochemical study using a polyclonal anti-SK3 antibody. SK3 protein is partly expressed at the cell membrane of normal sized fibers in myotonic dystrophy. Although SK3 channels are also expressed in muscles from polymyositis and amyotrophic lateral sclerosis, the positive staining is observed only in regenerating or denervated fibers. No expression of SK3 protein in a myotonic mouse (ADR) suggests that the increase in the SK3 channel in myotonic dystrophy is not due to hyperexcitability. These data support the hypothesis of a differentiation defect in myotonic dystrophy.