Treating mice with radioactive strontium, results in local irradiation of bone marrow and bone and the destruction of cellular elements which depend upon the micro-environment of the bone marrow for differentiation. Although T and B cell immunity and other hemopoietic cell functions appear to be relatively normal in these animals, a number of host resistance phenomena are markedly altered. Many of these normal host resistance events appear to be the result of alterations in the control of immune reactions. Recent studies in our laboratory have demonstrated that suppressor cells obtained from animals treated with 89Sr are easily activated and become immunosupressive in times and under conditions when normal immunosuppressive activity does not occur. It is our intention to determine what mechanism of control is altered by radiation of the bone marrow micro-environment. We will determine if there is cellular involvement in this loss of control and whether there are humoral immunoregulatory factors which have become altered. If a regulatory cell is involved we will try to determine what type or types of cells they are. It will be determined whether immunosuppressive cells become activated in response to a positive stimulus or rather an escape from a normally inhibitory control. Assay methods will include in vitro primary antibody response using the Mishell-Dutton assay system, adoptive transfer in inbred mice, and proliferative responses to mitogens.