In the present study, we have investigated the effects of phycocyanin, a biliprotein of Spirulina platensis, on mucosal and systemic immune responses and allergic inflammation in C3H/HeN and BALB/cA mice. To induce the antigen-specific antibodies in the peripheral lymphoid tissues such as Peyer's patches and mesenteric lymph nodes, biodegradable ovalbumin-entrapped poly (DL-lactide-co-glycolide) particles were used as an antigen. Two weeks after the onset of phycocyanin ingestion, mice were immunized with an aqueous ovalbumin (OVA) solution. Starting at one week after the primary immunization, the mice were subjected to oral immunization with the biodegradable OVA microparticles twice a week. IgA, IgE and IgG1 antibodies were determined by ELISA. The OVA microparticles of 4-microm diameter successfully induced antigen-specific antibodies. In the mice that received phycocyanin treatment for 6 wk, a marked increase in the antigen-specific, as well as the total, IgA antibody level was observed in the Peyer's patches, mesenteric lymph nodes and intestinal mucosa as well as in the spleen cells. Both antigen-specific IgG1 and IgE antibody levels in the serum were suppressed by ingestion of phycocyanin for 8 wk. However, inflammation of the small intestine, monitored as vascular permeability by the Evans blue-leaking method was reduced by phycocyanin at 6 wk, which preceded the suppression of antigen-specific IgG1 and IgE antibody production by 2 wk. These results suggest that phycocyanin enhances biological defense activity against infectious diseases through sustaining functions of the mucosal immune system and reduces allergic inflammation by the suppression of antigen-specific IgE antibody.