It is discussed why some, but not all HLA-B27-positive persons get disease when triggered by certain infections. The conclusions are that a possible modifying gene may be found on the other HLA haplotype or outside the HLA complex. Given an epidemic infection afflicting a family, it is the possible differences of other environmental factors which may be of interest, not a further description of the infection initially recognized. The familial clustering of disease is based upon modifying genetic factor(s) and/or environmental factor(s) shared by the family members. Timing of the environmental factors may be instrumental. Penetrance of genetic predisposition may also depend on coincidence of randomly occurring environmental factors.