Summary Alterations of microsatellites have been found at relatively high frequency in hereditary and sporadic colorectal cancer and gastric and pancreatic cancers and at lower frequency in some other cancers. We determined the frequency of instability at 39 poly-CA microsatellite loci in 20 squamous cell carcinomas and 26 Barrett's adenocarcinomas of the oesophagus. None of the tumours presented instability for a high percentage of the tested loci. Four squamous cell carcinomas and six Barrett's adenocarcinomas showed microsatellite instability at one locus, and three Barrett's adenocarcinomas showed microsatellite instability at two loci. The presence of few loci showing microsatellite instability could be due to an instability background. We conclude that genetic defects in the DNA mismatch repair system do not play an important role in oesophageal cancers.Keywords: microsatellite instability; cancer of the oesophagus; squamous cell carcinoma of the oesophagus; Barrett's adenocarcinoma; DNA mismatch repair system Recently a new class of genetic alterations in human tumours has been described Thibodeau et al, 1993). These appear at microsatellite loci that are short, repeated nucleotide sequences distributed within the normal genome. Alterations of microsatellites consist of the loss or gain of one or more repeat units in tumours compared with matched normal DNA and have been termed microsatellite instability (MI). MI was first described in colorectal cancer, in both hereditary non-polyposis colorectal cancer (HNPCC) and sporadic colorectal cancer cases Thibodeau et al, 1993), as a result of a deficient DNA mismatch repair system (Fishel et al, 1993;Leach et al, 1993;Parsons et al, 1993;Bronner et al, 1994;Papadopoulos et al, 1994). MI has also been observed in a variety of sporadic cancers, such as endometrium, stomach, kidney, ovary and pancreas cancers, belonging to the HNPCC tumour spectrum (Han et al, 1993;Peltomaki et al, 1993;Risinger et al, 1993). In bladder, breast and lung cancers, MI has been reported with variable frequency (Gonzalez-Zulueta et al, 1993;Merlo et al, 1994; Schridar et al, 1994). There are conflicting reports concerning the presence of MI in oesophageal cancers (Meltzer et al, 1994;Keller et al, 1995;Mironov et al, 1995;Nakashima et al, 1995;Gleeson et al, 1996). Cancer of the oesophagus is among the most common and severe malignant neoplasms in the world (Muller et al, 1990;Parkin et al, 1993). There are two main histological types of oesophageal cancer, squamous cell carcinoma (SCC) and Barrett's adenocarcinoma (BA). SCC is more frequent and is associated with alcohol and tobacco consumption in Western countries (Tomatis et al, 1990