In conclusion, we have shown that human surfactant is immunogenic and that circulating surfactant-antisurfactant immune complexes are detectable in the plasma from infants and in adults with RDS. We found these immune complexes regardless of whether exogenous surfactant was used in the individual treatment regimen. These immune complexes do not yet seem to cause disease in the short term. Long-term effects, if any, are unknown. Indications for surfactant replacement therapy in neonatal RDS are clear. Trials of exogenous surfactant are just beginning in adult RDS, and potential immunogenicity will be of even greater concern in these patients. In all such situations, potential for side effects must be balanced against therapeutic efficacy and the gravity of the disease. Our data indicate that surfactants, particularly heterologous surfactants, are potent immunogens. One cannot assume that using homologous or heterologous surfactants in patients with RDS will always be immunologically innocuous. Nonetheless, based on present data, moderately long-term follow-up (2 to 4 years), we are encouraged by our observation that no selective adverse effects attributable to human surfactant have been recognized, yet mortality from RDS in infants less than 30 weeks has been nearly cut in half.