Reducing the plasma S1P concentration or increasing the tissue S1P concentration inhibits AMD3100-mediated HPC mobilization. Groups of 6 mice treated with DOP or placebo for 3 days (A-B) or deficient in SK1 (C-D) were killed 1 hour after treatment with 10 mg/kg of AMD3100 or placebo. WBCs (A and C) and the number of CFUs present in cardiac blood (B and D) were determined as described in the “Methods. ” Representative data from 1 of 2 experiments are shown. #P < .05 compared with AMD3100 alone (B) or AMD3100-treated wild-type mice (D). ELISA was used to determine the level of S1P in the plasma of wild-type and SK1^−/− mice (E) and the mean and SD of 3-4 animals for each group is shown. The ability of the plasma from wild-type and SK1^−/− mice to induce the chemotaxis of HPCs was determined using a CFU assay to assess the population recovered from the lower chamber (F). *P < .05.