Three mouse genes encoding type 1 protein phosphatase isotypes alpha, gamma and delta were expressed in Schizosaccharomyces pombe cells under the control of the regulatable promoter nmt1. In the repressed state, basal expression of mouse genes was able to rescue the S. pombe mutant dis2-11. An integrated mouse gene could not, however, genetically complement S. pombe double mutants carrying disrupted dis2 and sds21 protein phosphatase genes. Overexpression of any of the three mouse protein phosphatase1 isotypes produced growth arrest and loss of viability in wild-type S. pombe cells. Overexpressing cells showed defects in chromosome distribution and in the formation of septa. These defects are characteristic of the expression of the mammalian protein phosphatases in S. pombe, since they are not observed after overexpression of endogenous S. pombe type 1 protein phosphatases. Overexpression of a truncated version of isotype delta, which lacked protein phosphatase activity, reproduced most of the characteristics of the lethal phenotype. We conclude that the lethal effect may be due to interactions with essential cell cycle proteins.