The dependence of septation on karyokinesis was studied in protoplasts of the fission yeast Schizosaccharomyces pombe. The mononuclear protoplast produces a single centrally located septum. In multinuclear reverting protoplasts, on the other hand, the formation of a single septum was a rare event. In each protoplast instead of one, two to six septa were formed. These findings suggest some closer relations between the formation of septa and the number of nuclei present in the protoplast. Our results obtained with protoplasts also imply that the initiation of septum formation is possible only in the presence of a complete cell wall. In reverting multinuclear protoplasts undergoing more than one mitosis, no septation is initiated until the cell wall has been completed. Only the complete cell wall can induce the formation of one or several septa in mono- and multinuclear protoplasts, respectively.