The effects of posture on the lymphatic outflow pressure and lymphatic return of albumin were examined in 10 volunteers. Lymph flow was stimulated with a bolus infusion of isotonic saline (0.9%, 12.6 ml/kg body wt) under four separate conditions: upright rest (Up), upright rest with lower body positive pressure (LBPP), supine rest (Sup), and supine rest with lower body negative pressure (LBNP). The increase in plasma albumin content (Alb) during the 2 h after bolus saline infusion was greater in Up than in LBPP: 82.9 ± 18.5 vs. 28.4 mg/kg body wt. Alb was greater in LBNP than in Sup: 92.6 vs. 22.5 ± 18.9 mg/kg body wt (P < 0.05). The greater Alb in Up and Sup with LBNP were associated with a lower estimated lymphatic outflow pressure on the basis of the difference in central venous pressure (CVP). During LBPP, CVP was increased compared with Up: 3.8 ± 1.4 vs. 1.2 ± 1.2 mmHg. During LBNP, CVP was reduced compared with Sup: 3.0 ± 2.2 vs. 1.7 ± 1.0 mmHg. The translocation of protein into the vascular space after bolus saline infusion reflects lymph return of protein and is higher in Up than in Sup. Modulation of CVP with LBPP or LBNP in Up and Sup, respectively, reversed the impact of posture on lymphatic outflow pressure. Thus posture-dependent changes in lymphatic protein transport are modulated by changes in CVP through its mechanical impact on lymphatic outflow pressure.