The thick and thin section technique was used to study guinea-pig megakaryocytes by electron microscopy, combined with either autoradiography or cytophotometric determination of DNA. Megakaryocytes engaged in polyploidization already showed granule formation, which began in the Golgi apparatus partially encircled by the nucleus. The ploidization phase stopped at the 8N, 16N or 32N level, after an average of 3 ± 0.5 (1 S.D.) genome duplications. Microtubules, myofibrils and demarcation membranes were also present in the immature megakaryocytes but organelles were formed in increasing amounts in non DNA-synthesizing cells. Platelet liberation, possible at the 8N, 16N or 32N stage, occurred in non DNA-synthesizing cells, principally at the 16N level.