The recent discovery of the cystic fibrosis gene enables DNA-based testing for the direct identification of the deletion of three basepairs coding for phenyalanine at codon 508, the major mutation responsible for the disease. This mutation can be detected by analysis of amplified DNA with allele-specific oligonucleotide probes. We have simplified the procedure of Kerem et al. (Science 1989;245:1073-80) so that the assay can be routinely completed in one working day, starting with an extracted DNA sample. Addition of salmon-sperm DNA to the product of the polymerase chain reaction greatly improved the quality of the hybridization signal. The precision of the method was evaluated by blind analysis and interpretation of results for 100 specimens from 25 patients. The same result was obtained for each patient analyzed separately four times, and four independent observers agreed on the interpretation of results for all 100 specimens. No specimen required repeat analysis to produce interpretable results. We conclude that this method is reliable and convenient for routine clinical laboratory use.