The efficacy of the polymerase chain reaction (PCR) in the first-trimester prenatal diagnosis of Duchenne muscular dystrophy (DMD) was examined. Twenty-seven fetuses from 26 Japanese pedigrees at risk for DMD were analyzed. PCR-restriction fragment length polymorphism analysis, multiplex PCR, and dinucleotide repeat polymorphism analysis were used. Of 16 males, 11 were determined to be unaffected, 4 were affected, and the remaining 1 was undetermined. Of the 11 female fetuses, 1 was diagnosed as a noncarrier, 4 were carriers, and the carrier status of the remaining 6 was not determined at the option of the patients, although DNA polymorphisms could be detected in those patients. Prenatal diagnosis by PCR analysis was possible in 96% of the fetuses tested (26 of 27).