The phosphotyrosine content of the cdc2 protein kinases, the catalytic component of maturation-promoting factor (MPF), is an important parameter of mitotic regulation in a variety of organisms. Recent studies have shed considerable light on how the cdc2-specific tyrosine kinase (wee1) and its competing phosphatase (cdc25) are regulated during the cell cycle. A goal for the future will be to obtain a comprehensive picture of how the wee1-cdc25 regulatory system collaborates with other steps in mitotic activation to ensure that cell division occurs at the appropriate time during the cell cycle.