The studies presented in this paper were undertaken to determine whether IgE- and IgG-producing murine B lymphocytes could be distinguished by differential resistance to x-irradiation in vivo. Sensitivity or resistance of B lymphocytes to various doses of x-irradiation was monitored by measuring the production by irradiated cells of haptenspecific IgG and IgE antibody. The results indicate that both primed and unprimed IgG B lymphocytes are less radioresistant than corresponding IgE B lymphocytes. Primed IgG B lymphocytes are more radioresistant than unprimed IgG B cells whereas unprimed IgE B lymphocytes are at least as radioresistant as primed IgE B lymphocytes. The relative radioresistance of primed IgE vs IgG B cells was best demonstrated in an adoptive transfer system. Thus, exposure of ASC-primed mice to 300 R 24 hr after transfer into these mice of syngeneic, DNP-KLH-primed spleen cells led to a sustained failure to produce IgG anti-DNP antibody after challenge with DNP-ASC; under these conditions IgE anti-DNP production was not impaired. This was shown to reflect differential radioresistance of the corresponding B cell populations. In addition, exposure to x-irradiation tended to augment IgE anti-DNP antibody responses when compared to unirradiated controls. This phenomenon is thought to reflect the effects of x-irradiation on regulatory mechanisms controlling the mouse IgE response and is explored in detail in an accompanying manuscript. The results described in this paper are discussed in the light of our evidence suggesting that, in both mouse and man, IgE B lymphocytes have certain unique characteristics by which they may be distinguished from other classes of B lymphocytes.