Mice fed a Spirulina platensis diet showed increased numbers of splenic antibody-producing cells in the primary immune response to sheep red blood cells (SRBC). However, immunoglobulin G (IgG)-antibody production in the secondary immune response was hardly affected. The percentage of phagocytic cells in peritoneal macrophages from the mice fed S. platensis diet, as well as the proliferation of spleen cells by either concanavalin A (Con A) or phytohemagglutinin (PHA) was significantly increased. Addition of a hot-water extract of S. platensis (SHW) to an in vitro culture of spleen cells markedly increased proliferation of these cells, whereas culture of thymus cells was scarcely affected. The Spirulina extract also significantly enhanced interleukin-1 (IL-1) production from peritoneal macrophages. Addition to the in vitro spleen cell culture of SHW as well as the supernatant of macrophages stimulated with SHW resulted in enhancement of antibody production, that is, an increase of the number of PFC. These results suggest that Spirulina enhances the immune response, particularly the primary response, by stimulating macrophage functions, phagocytosis, and IL-1 production.