As the prevalence of a disease decreases, so does the positive predictive value for testing for acute infection with that disease. Although documentation of IgG antibodies to rare infectious agents is useful (for documentation of effective vaccination, for example), assessing acute infection by evaluation of IgM antibody status to these agents is fraught with false positives and low predictive value. For example, according to the Centers for Disease Control and Prevention, rubella is no longer endemic in the United States. As such, nearly all positive rubella IgM antibody tests are false positives, resulting in unnecessary follow-up testing and unnecessary anxiety. Even for diseases not yet eradicated and for which low level outbreaks still occur (such as measles), if overall prevalence remains low, then the predictive value of positive IgM serology will still be low. False-positive measles IgM serology, for example, has been documented due to cross-reactivity to parvovirus and human herpes virus 6, among others. If clinical evaluation yields legitimate pretest suspicion for a rare infectious disease, then practitioners should report to and engage the help of their state public health department and/or the Centers for Disease Control and Prevention in further evaluating for potential acute infection. In common viral infections, it is also most effective to limit IgM serology to those cases in which clinical assessment yields relatively high suspicion for acute infection, since there are well-known causes for potential IgM antibody cross-reactivity (rheumatoid factor, cross-reactivity with other viral antigens). The potential for false-positive results will decrease (and positive predictive value will increase) with increasing pretest probability for true acute infection.