The interaction of antiparasitic drugs with the polymorphic cytochrome P450 2D6 was studied in human liver microsomes. Of ten different drugs tested, three quinolines, oxamniquine, primaquine and chloroquine inhibited microsomal CYP2D6-catalysed formation of 1'hydroxybufuralol at concentrations that might have clinical consequences in drug use. These drugs inhibited competitively bufuralol metabolism with Ki values of 22, 23 and 15 microM, respectively, indicative of high affinity for the CYP2D6-active site. The results imply that oxamniquine, primaquine and chloroquine could be substrates of cytochrome P4502 D6 or that they are potent non-substrate inhibitors of the enzyme similar to quinidine. In either case, the inhibition of CYP2D6 by these agents could lead to interference with in vivo population-phenotyping procedures in the tropical regions where treatment with the drugs is common.