Insight into how organisms adapt to environmental stimuli has become increasingly important in recent years for identifying key virulence factors in many species. The life cycle of many pathogenic nematode species forces the organism to experience environments which would otherwise be considered stressful. One of the conditions often encountered by nematodes is a change in environmental pH. Living in a soil environment Caenorhabditis elegans will naturally encounter fluctuations in external pH. Therefore, C. elegans has the potential to provide an insight into how pathogenic nematodes survive and proliferate in these environments. We found that C. elegans can maintain over 90% survival in pH conditions ranging from pH 3 to 10. This was unrelated to the non-specific protection provided by the cuticle. Global transcriptional analysis identified many genes, which were differentially regulated by pH. The gene cah-4 encodes two putative alpha carbonic anhydrases (CAH-4a and CAH-4b), one of which was five-fold up regulated in an alkaline environment (CAH-4b). Stopped-flow analysis of CAH-4b using 35 different carbonic anhydrase inhibitors identified complex benzenesulfonamide compounds as the most potent inhibitors (K(i) 35-89nM).