Human papillomavirus (HPV) may have a pathogenic role in squamous cell carcinoma of the oesophagus. Tylosis, an inherited thickening of the skin of the palms and soles, was associated with a high risk of developing squamous cell carcinoma of the oesophagus among members of a large family in Liverpool. The resected carcinomas of the oesophagus was examined from four such patients with DNA probes to HPV types 6,11,16,18,31,33 and 35 using in situ hybridisation under conditions of high stringency. No reaction was detected. The oesophageal biopsy specimens from 10 tylotic subjects without carcinoma were also examined. No HPV DNA was detected. It is concluded that there is no evidence that HPV infection has a role in the development of squamous cell carcinoma of the oesophagus in tylosis.