We have shown that administration of anti-C5 antibody to newborn mice heterozygous for C5 deficiency can suppress C5 levels for prolonged periods. This is analogous to antibody-induced immunoglobulin allotype and idiotype suppression. Only certain sources of anti-C5 are effective in suppression. Of the three antisera extensively tested in (SWR × RIII)F1 hybrids, A/He anti-RIII was the most effective, SWR anti-RIII was less effective, and SWR anti-DBA/1 was ineffective. Only certain strain combinations of F1 hybrids are susceptible to C5 suppression. C5 suppression was seen with (SWR × RIII)F1 hybrids but not (SWR × DBA/1)F1 hybrids. Kinetics of C5 suppression suggest a requirement for an active, ongoing process in the maintenance of low C5 levels.