We examined the ultrastructural changes occurring in a human megakaryocytic leukemia cell line, CMK11-5, in response to stimulation with prostaglandin E1 (PGE1). The addition of PGE1 to cultured cells dose-dependently caused vacuole enlargement, the development of cell surface projections, cell surface vacuole formation, and the release of a tracer protein (horseradish peroxidase) which had been incorporated into cytoplasmic granules. These morphological changes, which occurred parallel with [Ca2+]i mobilization in the CMK11-5 cells, were similar to those observed in CMK cells in response to stimulation with ADP, thrombin, and collagen. Our present findings suggest that PGE1 has a stimulatory effect on CMK11-5 cells through the induction of [Ca2+]i mobilization, and that the PGE1-induced transmembrane signaling system in megakaryocytes is completely different from that in platelets.