Background: The underlying cause of a urethral stricture can sometimes be obscure. It is possible that an injury to the urethra induces an immunological cascade that generates scar tissue and fibrosis, eventually resulting in a stricture. If such immunological reactions could be better elucidated, immunological therapies could possibly emerge. Objective: To evaluate if ectopic germinal centres exist in urethral stricture disease. Design, setting, and participants: Resected stricture specimens from 45 patients undergoing open bulbar urethroplasty with excision and anastomosis were assessed. Histopathological characteristics, such as fibrosis (grade I–III), inflammation, and sclerosis, were evaluated using immunostaining for CD3 (T cells), CD20 (B cells), and CD21 (follicular dendritic cells). Outcome measurements and statistical analysis: The primary outcome measure was the presence or absence of a germinal centre. The secondary outcome was evaluation of any correlation between the degree of fibrosis and germinal centres. Fisher’s exact test was used for univariate analysis. Results and limitations: In six patients, ectopic germinal centres were found. In ten patients, there was no inflammation at all. There was no correlation found between the degree of fibrosis and the abundance of immunohistochemically detected immune cells. Conclusions: Ectopic germinal centres, with B and T cells as well as follicular dendritic cell networks, do exist in urethral stricture disease. This finding may open up for novel research avenues on the possibility of adopting immunological treatments for urethral stricture disease. Patient summary: In patients with a narrowing of the urethra due to any kind of trauma, we looked for the presence of centres of immunological reaction in urethral tissue. We identified these immunological centres (also called germinal centres) in some patients. This intriguing finding suggests that immunological treatments may have potential for men with scar tissue in a narrowed urethra.