In four patients with cold agglutinins, erythrocyte mean corpuscular volume was increased. Erythrocyte volume histograms showed that in each case macrocytosis was due entirely to doublet erythrocytes counted as single cells. For two of the four patients, macrocytosis was reported intermittently, when the blood had been allowed to cool to room temperature during laboratory processing. For these two patients, macrocytosis due to doublet erythrocytes could be elicited in vitro proportionate to the degree of cooling of the blood and could be abolished to rewarming to 37 C. Two other patients had macrocytosis constantly during the acute illness. Otherwise unexplained macrocytosis may reflect cold agglutinin activity without overt hemolysis, particularly if the macrocytosis is intermittent.