The effect of halothane anesthesia on the humoral immune response to sheep red blood cells was studied in mice immunized twice, with a 15-day interval. On both occasions, mice were exposed to 1.5% halothane for 40 min immediately after sensitization. Halothane reexposure resulted in increased numbers of IgG-secreting cells (IgG-SC) as well as circulating 7S-serum agglutinins. To examine further whether this effect could be obtained in syngeneic recipients, adoptive transfer experiments employing spleen cells were performed. While mice receiving cells from unimmunized and anesthetized donors displayed significantly higher levels of IgG-SC, recipients of cells from normal, immunized and immunized-anesthetized donors showed a depressed response when compared to control counterparts. Besides the possibility of an enhancing effect of halothane reexposure on the humoral response, this procedure may counteract normal physiological immunoregulatory processes during the generation of the immune response.