1. The metabolism of six purified and radioiodinated cold agglutinins has been studied in five patients with chronic cold haemagglutinin disease and in six normal controls. Two of the patients showed overt haemolysis at the time of this study and all had complement components adsorbed to the surface of their red cells.
2. The mean fractional catabolic rate (FCR) of the cold agglutinins, studied in the patients from whom they were isolated (14·5%/day), was similar to the mean FCR of the same cold agglutinins in normal controls (15·6%/day) and there was no correlation between the FCR and the presence of haemolysis. Exposure to cold with a concomitant increase in haemolysis during the course of one of these studies had no effect on the catabolic rate of the cold agglutinin.
3. Individual values for the FCR ranged from 10·8 to 19·4%/day (corresponding to half-lives of 4·9–7·8 days) and appeared to be characteristic for each recipient. When two different cold agglutinins were studied simultaneously in the same subject their catabolism was virtually identical.
4. Untreated patients with chronic cold haemagglutinin disease were calculated to be synthesizing IgM at approximately ten times the normal rate. The fall in serum IgM concentration and agglutinin and haemolysin titres, following treatment with alkylating agents, appeared to be due to a diminution in the rate of synthesis and not due to increased catabolism.
5. ‘7S’ subunits of one of the cold agglutinins, which retained cold haemagglutinating activity, were rapidly catabolized in a normal subject.