A method is described for performing hemolytic plaque assays in microculture plates. The technique may be applied to assay in situ the antibody responses of cells cultured in these plates, or to assay the responses of cells obtained from other sources. The advantage of this method is that in comparison to conventional assays it is more economical both in terms of time and cost. Materials and Methods. Mice. BDF1 mice were obtained from Jackson Laboratories, Bar Harbor, Maine. They were used at 8 to 12 weeks of age. Antigens. Sheep red blood cells (SRBC) 2 were obtained from the Colorado Serum Co., Denver, Colo. Burro (BRBC) were obtained from Davis Laboratories, Davis, Calif. Cultures. Spleen cells were cultured by the methods of Mishell and Dutton (1) with either 35-mm Falcon disposable cultures dishes containing 106 to 107 cells in 1 ml of culture medium, or Falcon Microtest II culture plates containing 105 to 106 cells in 0.1 ml of culture medium.