The bitter-tasting compounds derived from the flowers of the hop plant (Humulus lupulus L.) protect beer from bacterial spoilage. However, a few lactic acid bacteria, especially lactobacilli, are resistant to these compounds and sometimes cause serious spoilage in the beer industry. It is important to elucidate the mechanisms of hop-resistance in lactic acid bacteria. We selected mutants of Lactobacillus brevis resistant to high concentrations of the hop compounds. The parental strain, L. brevis ABBC45, carries several plasmids. The copy number of one plasmid, termed pRH45, was remarkably increased in one of the hop-resistant mutants compared with that in the wild-type strain. pRH45 (15.0 kb) contains an open reading frame of 1749 b, termed horA, the deduced protein of which includes six putative transmembrane domains and an ATP-binding domain. The amino acid sequence of this putative protein is significantly homologous to half molecules of a mammalian multidrug resistance gene product, P-glycoprotein, and to several bacterial ABC transporters. Furthermore, the hop-resistant mutant was found to be weakly resistant to novobiocin and ethidium bromide, which are structurally and functionally unrelated to the hop compounds. A possible role of the potential drug efflux pump gene in the hop-resistance of L. brevis is discussed.