Rice blast, caused by Magnaporthe oryzae, is a devastating disease of rice (Oryza sativa). The mechanisms involved in resistance of rice to blast have been studied extensively and the rice--M. oryzae pathosystem has become a model for plant--microbe interaction studies. However, the mechanisms involved in nonhost resistance (NHR) of other plants to rice blast are still poorly understood. Here, we investigated interactions between Arabidopsis thaliana and M. oryzae to identify the genetic basis of NHR. In A. thaliana accessions, preinvasion resistance to M. oryzae in Col-0 was stronger than that of Ler. To examine the genetic basis underlying the natural variation in the responses, we used a well-established set of recombinant inbred lines (RIL) derived from a Col × Ler cross and identified three quantitative trait loci that govern the expression of NHR in A. thaliana against M. oryzae. Among the penetration (pen) mutants, only the pen2 mutant allowed increased penetration into epidermal cells by M. oryzae. Double mutant analysis indicated that AGB1 and PMR5 contribute to PEN2-mediated preinvasion resistance to M. oryzae in A. thaliana, suggesting a complex genetic network regulating the resistance. Our results demonstrate that A. thaliana can be used to study mechanisms of NHR to M. oryzae.