The first linkage to CF was demonstrated to the enzyme paroxonase, a classical protein polymorphism, by the Copenhagen group. This was followed quickly by six cloned DNA sequences: pJ3.11, 7C22, COL1A2 and TCRB (St. Mary's), 917 (Toronto) and met (Salt Lake City). Both pJ3.11 and met are very close genetically to the CF mutation, and can be used for carrier detection and antenatal diagnosis in many informative families where there is a CF child. There is no evidence for heterogeneity of the CF locus. The collection of markers surrounding the CF locus is now sufficient to permit attempts to be made to isolate the defective gene using a combination of chromosome-mediated gene transfer, pulse field gel electrophoresis, NotI junction libraries, cosmid mapping and chromosome walking techniques.