When limited amounts of antigens are available, it is often difficult to obtain large quantities of polyclonal antisera. Although antisera can be raised in small rodents, yields are usually small. To circumvent these problems, we have designed a modified method for generating polyclonal ascites fluid (AF). Using the appropriate strain of mice and adjuvant, we generated high serum titers by injection of 1-100 micrograms of protein. Following i.p. injection of compatible sarcoma cells, 13-19 ml of high titer (1:1000-1:20,000), polyclonal ascites fluid were obtained from each mouse. Similar results were obtained using nine different antigens.