Spindle orientation controls nuclear migration and segregation during mitosis. In yeast, defects in dynein and astral microtubules lead to abnormal spindle orientation and nuclear migration. Dynactin complex is necessary for dynein-mediated vesicle motility in vitro. The major polypeptide of dynactin complex is an actin-related protein in the family Arp1. We have identified in S. cerevisiae a novel actin-related gene, ACT5, in the Arp1 family. An act5 null mutant has defects in spindle orientation and nuclear migration, as does overexpression of Act5p. The phenotype of a double mutant lacking dynein and Act5p is similar to that of single mutants. Therefore, dynactin complex is in the same pathway as dynein and may be necessary for the action of dynein in vivo.