The expression of cell adhesion proteins is frequently deranged in bladder carcinomas. Since tissue transglutaminase (tTG) can increase cellular adhesiveness, its expression was studied in both superficial and invasive transitional cell carcinomas. No expression of tTG was found in normal urothelium or in grade 1-3 papillary tumours without invasion. Expression of tTG was seen in the invasive processes of five grade 3 tumours with microinvasion and in 49 of 63 solid grade 3 and 4 tumours. In six cases, both primary tumours and biopsies from liver metastases were studied. In all these cases, the liver metastases were tTG-negative, while the primary tumours were tTG-negative in five cases and consisted of both tTG-positive and tTG-negative cells in one case. Analysis of tTG protein in tumour extracts by Western blotting showed expression of the 77 kD tTG, with no evidence for expression of the truncated form found in some cell types. It is suggested that tTG, when expressed, contributes to the deranged adhesive properties of the carcinoma cells and may influence the course of invasion. These results also raise the possibility that lack of tTG expression may increase the risk of developing blood-borne metastases.