Summary The agglutinin titer of a mixture of sheep erythrocytes and the homologous agglutinin is significantly potentiated by the addition of certain animal sera including human. The magnitude of potentiation varies with different sera within species and is a function of dilution. The majority of the sera from patients with active peripheral rheumatoid arthritis potentiate the agglutinin titers to a higher degree than do the majority of sera from individuals with no evidence of this disease. The sera (85%) from patients with active peripheral rheumatoid arthritis are further and more specifically distinguished from the sera of other individuals. Combination of the sera of such rheumatoid patients with certain animal sera diluents, notably sheep, produce agglutinin titers significantly greater than those produced by the components of the mixture when tested alone in the same concentrations. The sera of a few individuals with other diseases (1.6%) also exhibit the phenomenon of potentiation in combination with sheep serum diluent. Procedures are described, based on potentiation of serum titers, which were found to have a high degree of sensitivity and specificity with sera from cases of active peripheral rheumatoid arthritis.