Neither lipophilicity nor vapor pressure of larger n-al-kanes appear to correlate with their anesthetizing partial pressures in inspired gas. Such results suggest that the Meyer-Overton hypothesis and Ferguson's rule may not apply to these compounnds. An alternative explanation might be that a large difference in inspiredto-arterial partial pressure exists, i.e., that the inspired partial pressure misrepresents the effective partial pressure. To test this explanation, we investigated the kinetics of five consecutive even-numbered n-alkanes (C2H6 to C10H22) in rats. The ratio of end-tidal-to-inspired (PA/P1), arterial-to-end-tidal (Pa/PA), and arterial-to-inspired (Pa/P1) pressures decreased with increasing carbon chain length, consistent with our separate finding that blood solubility increased. Using Pe/P1 and the minimum inspired concentration (MIC) obtaihed previously, we calculated the true effective potency, minimum alveolar anesthetic concentration (MAC); of these n-alkanes as (Pa/P1)(MIC). This markedly improved, but did not perfectly correct, the correlation of MAC with lipid solubility (the Meyer. Overton hypothesis) and vapor pressure (Ferguson's rule). A coefficient of variation of 76.7% was found for the product of MAC and the olive oil/gas partition coefficient. More importantly, the correlation of the logarithm of MAC and oil solubility had a slope of 0.724(i.e., deviated from-1.0), whereas the slope for eight conventional anesthetics was-1.046 (approached-1.0). These data imply that olive oil does not adequatelv mimic the nature of the anesthetic site of action of n-alkanes.