Infection of intact (nu/+) or hypothymic (nu/nu) BALB/c mice with the lethal intra-erythrocytic parasite, Babesia rodhaini, induced several changes in the surface proteins of red cells from infected blood. Lactoperoxidase-catalysed radio-iodination was used to compare the surface proteins on normal mouse erythrocytes and the total red cells from infected blood at different levels of parasitaemia. At very low parasitaemia, when only 2.5% of the red cells contained parasites, we observed significant changes in the profile of radio-iodinated proteins separated by SDS-polyacrylamide gel electrophoresis. These changes included the appearance of a group of high molecular weight proteins, and a protein with an apparent molecular weight (Mr) of 60 000, both of which were absent from normal erythrocytes. The major labelled band on the erythrocyte surface (Mr 92 000) also appeared to be less heavily labelled during infection. The magnitude of these differences in surface proteins increased as the parasitaemia rose, until the new bands dominated the radioactivity profile with blood of greater than 50% parasitaemia. Several control experiments established that the radio-iodinated proteins were surface molecules on intact cells and that artifactual proteolysis did not contribute to the observed differences. The results suggest that changes in the surface proteins occur on all red cells in the blood of infected mice. The results of labelling the surface glycoproteins by oxidation with periodate or galactose oxidase, followed by NaB3H4 reduction, have varied with the isolate of B. rodhaini. With the isolate currently in use, no significant differences were observed in the labelled surface glycoproteins of normal erythrocytes and red cells from infected blood of high parasitaemia, whereas an earlier isolate exhibited a marked decrease of glycoprotein labelling of both infected and uninfected red cells.