The autosomal dominant prealbumin amyloidoses are late‐onset disorders characterized by varying degrees of peripheral neuropathy, nephropathy and cardiomyopathy. To date, seven different single amino acid mutations in the plasma protein prealbumin (transthyretin) have been found to be associated with amyloidosis and each is the result of a single nucleotide change in the prealbumin gene. By virtue of the restriction endonuclease sites created by the point mutations which give rise to the protein variants, direct DNA tests using Southern analysis have already been developed for detection of the Met‐30, Ile‐33, Ala‐60, Tyr‐77 and Ser‐84 prealbumin genes. As an alternative to Southern analysis, we have amplified discrete regions of the prealbumin gene using polymerase chain reaction (PCR) and used restriction enzyme analysis of the PCR products to detect the Met‐30, Ala‐60, Tyr‐77 and Ser‐84 prealbumin genes after agarose gel electrophoresis and staining with ethidium bromide. In comparison to Southern analysis these alternative tests yield results much more quickly and avoid the use and handling of radioacti