Exchange transfusion with the oxygen-carrying resuscitation fluid, Fluosol DA 20% (FDA), interferes with the efficacy of penicillin therapy of pneumococcal infection in rats. Because this effect could not be attributed to an interaction between FDA and penicillin, the effect of FDA on the ability of rats to mount an antibody response to type 3 pneumococcal polysaccharide was tested. FDA (25 ml) was administered by isovolumetric exchange transfusion. Rats were immunized intravenously with 0.2 microgram of type 3 pneumococcal polysaccharide 3 days before, 1 day before, 1 day after, or 3 days after transfusion with FDA. IgM and IgG antibody responses were determined by ELISA 0, 3, 7, 10, 14, 21, and 28 days after immunization. When rats were immunized 3 days before or 1 day before transfusion with FDA, antibody levels were increased above control levels and remained relatively high through Day 28. When the animals were immunized 1 day after transfusion, antibody levels were approximately the same as in the control group. When the rats were immunized 3 days after transfusion, antibody levels were suppressed. These data suggest that FDA does not inhibit the humoral immune response when administered after or within 1 day before immunization, but does inhibit the response when immunization is given 3 days after transfusion.