THe interaction of pathogenic mycoplasmas with two components of the "nonspecific" defence system is influenced by the lack of a cell wall and perhaps the tight attachment to host cells. On mycoplasmas, complement can act directly on the parasite membrane surface and cause damage comparable to the effects on animal cells, namely lysis and death. Results with Mycoplasma pneumoniae suggest a direct activation by this species of the complement sequence without participation of homologous antibody. Activation may occur via the alternate pathway and perhaps even by direct triggering of the classical pathway. The action results in rounding, opsonization and death of some or all of the cells. Since complement components have been found in bronchial washings, this direct activation may be of some importance in the first stages of infection. Furthermore, it sufficiently explains the fact that M. pneumoniae is found only on the surface but not in the deeper tissues of the respiratory tract even in severe infections. The interactions of mycoplasmas with phagocytes, one of the first lines of defence against infection, is of considerable interest. Mycoplasmas seem to be relatively resistant to phagocytosis as long as they are not opsonized. They have been observed attaching to macrophage surfaces without being ingested. Addition of homologous antibody triggered immediate engulfment and intracellular killing. The aspects of interaction of phagocytes with mycoplasmas are even more interesting because in most cases the mycoplasmas which have to be phagocytized are attached to the surface of other tissue cells. This raises the problem of secondary damage caused by the enzymes of the phagocytizing cell. Our knowledge about the mycoplasma-phagocyte-interaction is scarce and the experimental approaches are difficult.