Serum interleukin-2 receptor (sIL-2R) levels have been used to assess immune activation in inflammatory and infectious illnesses, although the cellular origin of these receptors and the dynamics of their production are not well defined. To investigate the relationship between sIL-2R levels and the degree of immune activation in antigen-specific responses, sIL-2R were measured in healthy individuals after both primary and secondary immunization with keyhole limpet hemocyanin (KLH). Despite induction of strong antibody responses, KLH immunization did not result in consistent elevations of sIL-2R levels, with only one of six subjects developing a substantial (twofold) increase in sIL-2R levels. The absence of sIL-2R elevation after a discrete antigenic stimulus suggests that inflammatory illnesses in which elevated sIL-2R levels have been noted involve more extensive stimulation of immune cells, either in number or in degree, than that present after simple immunization in healthy individuals.