The cutoff phenomenon associated with the effectiveness of long-chain alcohols in the induction of anesthesia is also observed for various antimicrobial activities, although the mechanism has remained unknown for over eight decades. The minimum inhibitory concentrations at 25°C for budding yeast growth exponentially decreased with increasing chain length of n-alcohols (C 2-C 12), whereas alcohols $C 13 lost the inhibitory effect. Thus, growth inhibition by n-alcohols obeys the Meyer-Overton correlation up to C 12 and exhibits a cutoff phenomenon. The densities of n-alcohols are low, and the melting point and hydrophobicity increase with chain length. C 13 and C 14 inhibited yeast growth at 39.8°C, above their melting points. Alcohols #C 14 inhibited thermophilic bacterial growth at 50°C, whereas C 16 inhibited it at 67.5°C, above their melting points. Thus, the high melting points of long-chain alcohols contribute to the cutoff phenomenon. C 14 did not effectively inhibit yeast growth in a static culture at 39.8°C, in contrast to a shaking culture, in which the low density-dependent concentration gradient was eliminated. The duration of the transient growth inhibition of yeast by C 12 was prolonged by sonication, which prevented hydrophobic aggregation. Therefore, a nonuniform distribution owing to low density and high hydrophobicity contributes to the cutoff. C 14 inhibited the growth at 25°C of the pdr1,3,5 mutant, defective in multidrug efflux pumps, whereas C 12 did not inhibit the growth of yeast overexpressing PDR5, indicating that the sensitivity to long-chain alcohols contributed to the cutoff. A balance between the physicochemical solubility of and the biological sensitivity to long-chain alcohols determines the cutoff chain length.