Overall inhomogeneity of ventilation distribution, as measured by single-breath vital capacity (VC) washout (SBW) is known to be greater supine vs. standing. To establish the underlying mechanisms 13 healthy males performed VC SBW of 4% SF(6) and He, standing and supine, with or without a 10 sec breathhold (BH). Overall inhomogeneity, as indicated by normalized phase III slopes, was >50% greater supine (SF(6) 13.1 x 10(-3); He 10.7 x 10(-3) L(-1)) than standing (SF(6) 8.6 x 10(-3); He 6.4 x 10(-3) L(-1); P<0.001). The (SF(6)-He) slope, an index of intraacinar inhomogeneity, did not change with posture. Breathholding, assumed to eliminate convective dependent inhomogeneity within and/or between small lung units, produced twice as great reduction of inhomogeneity when supine vs. standing. After BH inhomogeneity remained significantly greater supine vs. standing. In conclusion, at least two events seem to underlie the increased inhomogeneity when supine: (1) a substantially increased convection dependent non-uniformity between well-separated lung regions; and (2) a somewhat increased convection dependent non-uniformity within and/or between peripherally located lung units.