The mutation described here has been detected in the DNA of a female cystic fibrosis (CF) patient born in May 1963. CF has been diagnosed only at the age of 30 years and has been confirmed by three positive sweat tests. She does not require supplementation with pancreatic enzymes and her pulmonary function is unknown. The patient tested negative for the main mutation AF508 (Wagner et al., 1992); therefore, the individual CFTR exons have been screened for base alterations by denaturing gradient gel electrophoresis (DGGE) as described previously by Fanen et al. (1992). A shift detected in the exon 4 polymerase chain reaction (PCR) product was further analyzed by the direct solid-phase sequencing method (Hultman et al., 1989) using the following primers: S'-TGTG?TGAAATTCTCAGGGT and 5'-biotin CAGAATATATGTGCCATGGG. The sequencing analysis of the PCR product revealed one base pair deletion at position 460 of the nucleotide sequence of the CFTR gene (460delG). This results in a frameshift mutation that introduces TGA termination codon at position 123 of the polypeptide and may lead to production of a truncated or unstable protein. As the parents have not been available for analysis, we were unable to determine the haplotype of the CF chromosome carrying the allele and the segregation phase of the allele. The mutation is rare in our population since the characteristic DGGE migration pattern of the amplification product has been found only once in 200 non-A508 chromosomes from our CF population. CF mutation on the second chromosome of the patient is unknown.