Several recent reports raised the possibility that the target for the action of C (particularly the late acting components) in the cell membrane may be lipids or phospholipids. We have postulated that under certain conditions (e.g., after partial activation) C action could be inhibited by lipids found in cell membranes. The following lipids were tested: phosphatidyl glycerol (PG), cardiolipin (CL), cholesteryl esters (CE), phosphatidyl serine (PS), phosphatidyl ethanolamine mammalian (PEm) or bacterial (PEb), sphingomyelin (SP), cholesterol (CH), triglyceride, or phosphatidic acid. Lipids were mixed into VBS-gelatin and sonicated until a stable suspension was obtained. From dose response and kinetic studies we determined that about 10 min incubation of C at 0°C with 30 µg of lipids was appropriate for screening for inhibiting activity. The following pattern of inhibition of lysis emerged: 1) lysis of EA by limiting HuC and GPC: human C, no inhibition; GPC: whole C and C1̄ by PG only; C8, C9, no inhibition.