A series of hydroxyacetophenones was prepared for evaluation as leukotriene B4 (LTB4) receptor antagonists, culminating in l-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(lR-tetrazol-5-yl) heptyl] oxy] phenyl] ethanone (compound 35, LY255283). Using an assay for inhibition of specific [3H] LTB4 binding to human PMN, we found that substitution of a nonpolar substituent in the 5-position was required for activity. Best activity was realized with hydrogen in the 3-position, hydroxyl in the 2-position, short chain alkyl ketone in the 1-position, and a six-or eight-carbon chain linking theoxygen in the 4-position with an unsaturated terminal function. Compound 35, having an ICr, of 87 nM in the binding assay, was chosen for further preclinical evaluation.