Immunological unresponsiveness to soluble protein antigens has been studied in the domestic fowl using bovine gamma globulin (BGG) and bovine serum albumin (BSA). (SECTION C) Because the serological behaviour of chicken precipitating antibody differs antibody from that of typical mammalian antibody, it was necessary to undertake a preliminary investigation of the chicken anti-BSA and anti-BGG precipitin systems. Both systems were studied by carrying out quantitative precipitin tests and analysing the precipitates for total N and antigen N, Use of 131I-trace-labelled antigen in these tests made it possible to extend the analyses into the region of considerable antigen excess. (i) Neither system exhibited a well defined peak of maximal precipitation but produced a broad plateau over that region, (ii) No true equivalence point could be established for in moderate antibody excess precipitation of antigen was incomplete, (iii) The peculiarities of chicken antisera raise analytical difficulties that are most easily overcome by the use of labelled reagents (iv) A rapid method for the determination of the precipitin content of chicken antisera, using 131I-trace-labelled antigen, is described. It depends upon determination of the percentage of added antigen precipitated at the point of maximal precipitation. (SEDTION D) Although the chicken is a very good producer: of precipitins to native serum, proteins this immunological ability does not seem to extend to chemically altered antigens. In two experiments in which chickens were immunised with 3 different forms of chemically altered B3A only feeble antibody responses were elicited, even after 3 intravenous injections. (SECTION E) To study immunological unresponsiveness to soluble protein antigens both embryos and newly hatched chicks were injected with varying amounts of BGG or B3A, Only with difficulty was unresponsiveness induced, the best results being obtained by giving repeated doses of large amounts (100 mg) of antigen during the first few weeks of life. The results verify the general observations that the duration of unresponsiveness is finite and related to the amount of antigen given in early life to induce it, and that maintenance of the unresponsive state depends upon persistence of antigen. The greater difficulty experienced in making chickens unresponsive to BSA compared to the rabbit and mouse appears to be directly related to the very rapid elimination of BEA by the chicken. The need for further quantitative studies of unresponsiveness is stressed and a method that is; considered suitable for the measurement of a standard degree, of responsiveness is proposed. The chicken is suggested as a useful experimental animal for the type of quantitative study envisaged. (SECTION F) The effect of a cytotoxic drug, 6-mercaptopicrine on precipitin production in the adult fowl, was investigated. This purine analogue has been reported capable of causing a complete specific suppression of antibody response to BSA in the rabbit if given as daily doses during period of primary immunisation, even when the drug was administered at a level three times as great as that known to be effective in rabbits the antibody production of treated birds was equal to that of untreated contols. The failure of 6-MP to suppress antibody formation in the chicken may be due to the particularly vigorous production of precipitins by this species or to a more rapid catabolism and excretion of the drug by the fowl.