We describe the implementation of a modified version of the reverse dot blot hybridization technology to detect eight cystic fibrosis mutations. The method is simple, quick, reliable, inexpensive, and nonradioactive and utilizes the sensitivity of the polymerase chain reaction coupled with colored or chemiluminescent substrates for mutation detection. We have used this system in a clinical laboratory to identify the delta F508, G542X, G551D, R553X, 621 + 1G----T, W1282X, N1303K, and 1717G----A mutations. The technique is practical for genotyping individuals at many potential mutation sites, as in cystic fibrosis and beta-thalassemia, in which over 95 mutations can cause disease. This technology appears to be the method of choice for the widespread carrier screening of multiple cystic fibrosis mutations.