Lysis of virus-infected cells by human serum requires both IgG antibody to the virus and an intact alternative complement pathway. It has been shown that in the presence of antibody, serum either immunoehemically depleted of C4 or genetically deficient in C2 can lyse virus-infected cells, whereas factor-B-depleted serum cannot. In these studies either anti-viral IgG or its F(ab')2 fragment induced lysis in serum, whereas its Fab' fragment did not (1, 2). These observations were made with a variety of RNA-and DNA-budding viruses, and a range of human sera containing antibody to virus, suggesting that this might be a mechanism of wide biological applicability and relevance for clearing virus-infected cells.It has recently been shown that an intact alternative pathway of complement activation can be assembled from six isolated plasma proteins: C3, factors B and D, fllH, C3b inactivator (C3bINA), 1 and properdin (P) (3). Combination of the above six proteins and the five proteins of the membrane-attack pathway of complement ((25, C6, C7, C8, and C9) at their respective physiological concentrations, led to the formation of a cytolytically active alternative pathway whose function was qualitatively and quantitatively identical to the alternative pathway in serum. The isolated cytolytic alternative pathway was capable of lysing rabbit erythrocytes (4) and, upon addition of lysozyme, certain strains of Esherichia coli (5) with an efficiency virtually identical to C4-depleted human serum.The availability of the isolated cytolytic alternative pathway allowed us to definitively examine the complement-dependent lysis of antibody-coated measles virus- Abbreviations used in this paper: C3bINA, C3b inactivator; IAP, isolated alternative pathway; ICAP, isolated cytolytic alternative pathway; MEM, minimal essential Eagle's medium supplemented with 10% fetal bovine serum, glutamine, and antibiotics; P, properdin; SDS, sodium dodecyl sulfate; VBS, Veronalbuffered saline; VBS +÷ OVA, Veronal-buffered saline with 1.2 mM MgCI2, 0.15 mM CaCI2, and 0.1% ovalbumin. J. ExP. MED.