In fission yeast, the initiation of mitosis is regulated by a control network that integrates the opposing activities of mitotic inducers and inhibitors. To evaluate whether this control system is likely to be conserved among eukaryotes, we have investigated whether a similar mitotic control operates in the distantly related budding yeast S. cerevisiae. We have found that the protein kinase encoded by the mitotic inhibitor gene wee1+ of fission yeast, which acts to delay mitosis, is able also to delay the initiation of mitosis when expressed in S. cerevisiae. The wee1+ activity is counteracted in S. cerevisiae by the gene product of MIH1, a newly identified gene capable of encoding a protein of MW 54,000, which is a structural and functional homolog of the cdc25+ mitotic inducer of fission yeast. Expression of wee1+ in a mih1- strain prevents the initiation of mitosis. These data indicate that important features of the cdc25+-wee1+ mitotic control network identified in S. pombe are conserved in S. cerevisiae, and therefore are also likely to be generally conserved among eukaryotic organisms.