Pneumocystis carinii infection was produced in normal mice by the administration of corticosteroids and in athymic mice by the transmission of exogenous mouse- or rat-derived organisms. Serum antibodies to P. carinii, measured by an indirect fluorescent-antibody technique, were found in five of six strains of normal mice. Although antibody titers varied widely among the control and steroid-treated mice, they were inversely proportional to the intensity of P. carinii infection in the lungs. In sequential studies, antibody titers were low during steroid administration but rose with steroid withdrawal. Antibodies were mainly of the immunoglobulin G (IgG) class; IgM antibodies also occurred, but IgA antibodies were rare. nu/nu mice rarely produced serum antibodies to P. carinii despite the fact that one strain was sensitive and the other was resistant to exogenous infection. nu/+ mice produced specific antibodies to rat and mouse P. carinii which were primarily IgG. Thus, the host produces antibodies to P. carinii which are mainly IgG and T-cell dependent; yet, these antibodies do not appear to be important in susceptibility or resistance to P. carinii infection.