In this report, we detail changes in the expression of CD38 on murine B cells during the course of a T cell-dependent immune response. CD38 is expressed on all naive B cells but is down-regulated on isotype-switched B cells from both the germinal centers (GCs) and the foci of Ab-forming cells which arise during the first weeks of the response. The down-regulation on GC B cells, however, is reversible since Ag-specific IgG1 B cells with high levels of CD38 are apparent by 2 wk postimmunization. These cells have characteristics that resemble recirculating memory B cells, in that they are small and bind low levels of peanut agglutinin. Such characteristics indicate that the restoration of CD38 levels is coincidental with the transition from GC to memory B cell. Using this observation, we plotted the development of the memory population and the demise of the GC reaction as a function of time after immunization. Our results indicate that the GC reaction ceases gradually over many weeks rather than suddenly, which corresponds with the formation of the memory B cell population. Furthermore, by segregating memory B cells and GC B cells, it was possible to assess the in vitro survival characteristics of each compared with naive B cells. These experiments demonstrated that memory B cell survival in vitro was comparable with naive B cell survival but less than the survival seen for bcl-2-transgenic B cells, whereas GC B cell survival, as expected, was very poor. Hence, by resolving murine Ag-specific memory B cells and GC B cells, we have been able to quantify the development of the memory B cell population.