Two-dimensional (2-D) DNA typing is based on electrophoretic separation of genomic DNA fragments in two dimensions according to independent criteria (size and base-pair sequence), followed by hybridization analysis using multilocus probes. The technique allows simultaneous visualization of several hundred loci as spots in a 2-D pattern. The majority of the loci resolved are polymorphic. Using linkage analysis in a large CEPH family, this study reports the mapping of 34 loci detected by the minisatellite core probe 33.6. By multipoint linkage analysis, regional chromosome positions of the 33.6 loci could be deduced, showing no evidence of clustering. In the analysis of spot patterns, use was made of a computerized image analysis system specifically designed for 2-D DNA typing. Since experimental variations between different separation patterns were automatically corrected for with this program, rapid and reliable scorings could be obtained. The results presented demonstrate the availability of reliable genetic information throughout the 2-D separation pattern. Adding the use of semiautomated computerized pattern analysis, this study further substantiates the applicability of 2-D DNA typing in genome scanning, not only in theoretical but also in practical terms. Moreover, it can be anticipated that this method will have a specific advantage in studies that scan for trinucleotide repeat expansions and somatic instability, where the repeat sequences detected by appropriate core probes are of particular interest.