Cold agglutinin levels were determined in 120 individuals ranging in age from 1 to 64 years using untreated and ficin-treated group O erythrocytes. The geometric mean titer for untreated cells was 5.7 ±1.1 SEM and for ficin-treated cells 18.7 ±1.1 SEM. The mean titers and scores for various blood groups were not significantly different. Titers and scores correlated significantly to total serum IgM concentration (pcO.OOl). Females had significantly higher cold agglutinin levels than males (p<0.001). A significant decrease of cold agglutinins occurred in the 26- to 64-year age group as compared to the 11- to 25-year age group (p<0.01). The data should contribute to a clearer understanding of the biological impact of cold agglutinins.