Recent studies have shown that long-term hypoxia causes decreased platelet counts in mice and short-term hypoxia increased platelet counts. In an attempt to explain the mechanism that increases platelet counts of mice after exposure to short-term hypoxia, we measured platelet counts, total circulating platelet counts (TCPC), total circulating platelet masses (TCPM), percentages of 35S incorporation, and platelet sizes. Platelet counts, as well as TCPC and TCPM of mice, increased after 1–3 days of hypoxia, but these values were decreased after 6–7 days of hypoxia. Although platelet counts were increased in hypoxic mice, the percentage 35S incorporation into platelets and platelet sizes did not show a concurrent increase. After 6 days of hypoxia, average platelet diameters began to increase as platelet counts decreased. Splenic release did not account for the increase in platelet counts of mice after short-term hypoxia. It seems possible, therefore, that megakaryocytes “shed” platelets into the circulation in response to hypoxia. The platelets that enter the circulation in response to short-term hypoxia are smaller and incorporate less 35S than platelets that are produced in response to acute thrombocytopenia.