Four patients aged 62 to 78 years with the cold agglutinin syndrome have been treated intermittently or continuously with chlorambucil for one to seven years. This resulted in a decreased susceptibility to the cold so that Raynaud phenomena and hemoglobinuria were avoided in the winter. The hemoglobin value increased, the concentration of IgM-globulin in serum was nearly normalized, and the cold agglutinin titre decreased by a factor 3-30. The thermal amplitude was lowered by 2.2-7.2°C.