Effect of wortmannin, an inhibitor of phosphatidylinositol 3-kinase, on the first mitotic divisions of the fertilized sea urchin egg. We have reported earlier that the polyphosphoinositide messenger system may control mitosis in sea urchin eggs. Besides phospholipase C activation and its second messengers, phosphatidylinositol (PI) 3-kinase has been proposed to affect a wide variety of cellular processes in other cellular systems. Therefore, we have investigated whether PI 3-kinase could play a role in regulating the sea urchin early embryonic development. Our data presented here suggest that PI 3-kinase is present in sea urchin eggs. We found that wortmannin, an inhibitor of PI 3-kinase, led to arrest of the cell cycle. Chromosome condensation, nuclear envelope breakdown, microtubular aster polymerization, protein and DNA synthesis were not affected when fertilization was performed in the presence of the drug. However, maturation-promoting factor (MPF) activation was inhibited and centrosome duplication was perturbed preventing the formation of a bipolar mitotic spindle in wortmannin treated eggs. We discuss how PI 3-kinase might be involved in the cascade of events leading to the first mitotic divisions of the fertilized sea urchin egg.