Antigen stimulated changes in cyclic AMP levels which are the result of increases in prostaglandin levels, were measured by immunofluorescence in frozen spleen sections. The results provide direct visual confirmation of previous reports in that an increase in the number of cells staining positively for cyclic AMP were detected. The increase in cyclic AMP levels occurs in approximately 40% of the cells in the cortical region of the spleen. No staining was observed in deeper regions. Using sRBC as a particulate antigen and DNP-BGG as a soluble antigen, it was possible to show that a slightly smaller increase in the number of cyclic AMP positive cells occurs using DNP-BGG compared to sRBC. These data mean that antigen stimulated changes in splenic AMP levels occurs in a much larger population than could be accounted for on the basis of antigenic specificity. Such a result is consistent with previous data showing the increase in cAMP is a result of a prior increase in prostaglandin. Thus, any cell bearing a prostaglandin receptor could respond by showing an elevated cAMP level.