To examine the role of the human HLA class I molecule B27 in the direct interaction of yersinia and human cells we performed experimental infections of constitutive HLA B27-positive and -negative human fibroblast monolayers with Yersinia enterocolitica O.3. The numbers of yersiniae invading HLA B27-positive cells were within the range of HLA B27-negative cells. Treatment of fibroblasts with interferon-γ (IFN-γ) to enhance HLA B27 expression did not alter invasion. IFN-γ reduced titers of live intracellular bacteria, but not bacterial antigens, in a dose-dependent manner. Persistent infection with yersinia could be maintained for up to 10 weeks with decreasing bacterial titers and more slowly decreasing amounts of yersinial antigens in HLA B27-positive and -negative cells. Endogenous HLA B27 does not modulate the direct interaction of yersiniae with primary human fibroblasts. This is in contrast to infection of HLA B27-transfected murine cells. The protective effect of IFN-γ for yersinia-infected cells may be important for controlling complications in patients with yersiniosis.