Methylprednisolone sodium succinate limited the ability of zymosan or lipopolysaccharide to activate complement in normal serum by the alternative amplification pathways. Methylprednisolone limited B consumption in a reaction mixture which contained purified C3b, D, and B, indicating that soluble steroid directly inhibited the amplification pathway. The ability of soluble steroid to inhibit events in the alternative and amplification pathways of complement may provide a partial explanation for the effectiveness of steroids in treating gram negative septic shock.