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The inheritance of virulence in Bremia lactucae to match specific resistance factors in lettuce was studied by crossing heterothallic isolates of B. lactucae. Avirulence seemed to be dominant to virulence. Although virulence to some R-factors was inherited at a single locus, thus supporting the hypothesis of a gene-for-gene interaction between B. lactucae and L. sativa, inheritance of virulence to other R-factors was more complex. Two loci seemed to determine virulence to R11; the determinants of virulence to R5, R8 and R10 were either closely linked or allelic; virulence to these loci appeared to be epistatic to virulence to match R9. Virulence to R4 probably involved the interaction of two loci, one of which inhibited avirulence. Determinants of fitness of B. lactucae and possibly genes of minor effect modifying specific virulence factors also segregated. These studies emphasized the potential variability in B. lactucae and implied that isolates should not be assigned to distinct races.