The applicability of the crocin bleaching assay (CBA) to structure-activity relationship (SAR) studies of a great number (n = 39) of selected phenolic compounds was thoroughly investigated. The focus was on the activity of hydroxybenzoic, hydroxyphenylacetic, hydroxyphenylpropanoic, and hydroxycinnamic acids. Other assays [oxygen radical absorbance capacity (ORAC), lipid oxidation] were applied when necessary. Hydroxybenzoic acids were less active than the respective simple phenols. The position of the -COOH group relative to hydroxyl substituents was critical. The number and position of the -OH groups governed the order and size of activity within the subgroup of these acids. Gallic acid was the most active, being 1.6- and 3.4-fold superior to protocatechuic and syringic acids, respectively. The effect of proximity of the -COOH group to the phenyl ring was more distinct for 3,4-guaiacol acids (ferulic >> dihydroferulic congruent with homovanillic > vanillic) than for 3,4-catechol ones (caffeic >> protocatechuic > or = dihydrocaffeic congruent with homoprotocatechuic). Compounds such as vanillin, tyrosol, ferulic acid derivatives, rosmarinic acid, and quercetin were examined to reinforce discussion on the basis of physical organic chemistry principles. Taking into account the acidity of most compounds, the CBA-derived order of activity was meaningful.