In its natural habitat, the nematode Caenorhabditis elegans encounters a plethora of other organisms, including many that are pathogenic [ 1 ; 2]. The study of interactions between C. elegans and various pathogens has contributed to characterizing key mechanisms of innate immunity [ 2; 3 ; 4]. However, how C. elegans recognizes different pathogens to mount pathogen-specific immune responses remains still largely unknown [ 3; 5; 6; 7 ; 8]. Expanding the range of known C. elegans-infecting pathogens and characterizing novel pathogen-specific immune responses are key steps toward answering this question. We report here that the oomycete Myzocytiopsis humicola is a natural pathogen of C. elegans, and we describe its infection strategy. We identify a new host immune response to pathogen exposure that involves induction of members of a previously uncharacterized gene family encoding chitinase-like (CHIL) proteins. We demonstrate that this response is highly specific against M. humicola and antagonizes the infection. We propose that CHIL proteins may diminish the ability of the oomycete to infect by hindering pathogen attachment to the host cuticle. This work expands our knowledge of natural eukaryotic pathogens of C. elegans and introduces a new pathosystem to address how animal hosts recognize and respond to oomycete infections.