SummaryA rapid, robust and reproducible method providing excellent separation performance and simplicity using a 0.5 % MC-4000 methyl cellulosic sieving medium in DB-1 coated capillaries has been developed. The method is suitable for qualitative comparison of DNA restriction profiles for fragments in the size range 100-1000 base pairs (bp). Efficiencies up to 8.5 million plates/m (1057 bp fragment) were recorded. Peak resolution of 6 bp (291/297 bp, 335/341 bp) and 4 bp (238/242 bp, 341/345 bp) was achieved. In addition, 1 bp partial resolution of 123/124 bp and 298/297 bp was obtained. Run-to-run (n = 15), day-to-day (n = 4), and capillary-to-capillary (n = 3) variations of 0.1-0.2 % RSD, 0.3-0.5 % RSD, and 0.1-0.3 % RSD, respectively, were observed. The MC-4000 sieving matrix was found to be better than hydroxypropyl methyl cellulose and hydroxypropyl cellulose, in terms of both performance and stability in the DB-1 coated capillaries. The efficiency and resolution in DB-WAX capillaries were inferior to those obtained in DB-1 capillaries. The commercially available DB-1 capillaries were stable for months in the sieving medium at pH 8.3 and could be regenerated to provide high efficiency after accidental current breaks.