The functional characteristics of peritoneal cells (PC's) acquired in response to infection with Nematospiroides dubius were studied to identify changes which could be associated with the high level, long-term survival of this parasite or explain its transient immunosuppressive properties. The number of cells in the peritoneal cavity increased steadily during the infection, and the population displayed a transient hyperresponsiveness to inflammatory stimulation. N. dubius did not affect the ability of antigen-pulsed PC's to induce humoral responses or delayed-type hypersensitivity (DTH) in primed recipients, but lymphoproliferative responses induced in vitro were depressed by PC's from infected donors. In addition, unpulsed PC's from N. dubius-infected mice depressed proliferative responses to parasite antigens by autologous mesenteric lymph node cells. These effects are attributable to increased lymphocytostatic activity in the PC's, which peaked one week after infection and correlated with the expansion of a population of large plastic-adherent vacuolated cells with elevated acid phosphatase activity (activated macrophages). Comparable inhibitory cells did not develop in the same period of time during a short-lived infection with Nippostrongylus brasiliensis.