We used electron microscopic immunocytochemistry to study the distribution of calmodulin in rat sciatic nerve. Calmodulin immunoreactivity was found throughout the axoplasmic matrix, but particularly along microtubules. Schwann cell cytoplasm and nuclei demonstrated immunoreactivity, while compact myelin did not. There was particularly intense immuno-gold deposition within Schmidt Lanterman clefts. At the nodes of Ranvier, calmodulin appeared preferentially in the paranodal region, along the apposition of the axolemma to the paranodal loops of myelin and extending into the paranodal loops. The presence of calmodulin immunoreactivity along microtubules supports biochemical and pharmacological evidence of calmodulin involvement in regulating the assembly and phosphorylation of microtubules, and in fast axonal transport along microtubules. The co-localization of paranodal calmodulin immunoreactivity with Ca-ATPase activity demonstrated cytochemically (Mata et al., Brain Research, in press) supports the notion that the paranodal Ca-ATPase activity may be regulated by calmodulin, and agrees with the in vitro biochemical evidence for Ca-ATPase of other cells.