The amplification-refractory mutation system (ARMS) is a simple method for detecting any mutation involving single base changes or small deletions. ARMS is based on the use of sequence-specific PCR primers that allow amplification of test DNA only when the target allele is contained within the sample. Following an ARMS reaction the presence or absence of a PCR product is diagnostic for the presence or absence of the target allele. The protocols detailed here outline methods that can be used to analyze human genomic DNA for one or more mutations. The Basic Protocol describes the development and application of an ARMS test for a single mutation; the Alternate Protocol extends this to multiplex ARMS for the analysis of two or more mutations. The Support Protocol describes a rapid DNA extraction method from blood or mouthwash samples that yields DNA compatible with the type of tests described. The amplification-refractory mutation system (ARMS) is a simple method for detecting any mutation involving single base change The amplification-refractory mutation system (ARMS) is a simple method for detecting any mutation involving single base change.