Purified cleavage products of the guinea-pig complement component C3, namely C3b and C3a, interact with guinea-pig and mouse macrophages in culture to induce a dose- and time dependent release of lysosmal enzymes into the medium. In the case of C3b the selectivity of the release of hydrolases, which occurs without cell killing, is shown by morphological observations and the failure of lactate dehydrogenase to appear in the medium. However, lysosomal enzyme release in the presence of C3a is accompanied by loss of cellular lactate dehydrogenase. Preincubation of C3b with anti-C3 Fab inhibits its attachment to macrophages, after which there is hardly detectable enzyme release into the medium. We have found that stimulated macrophages release enzyme(s) which can cleave C3, generating more C3b either directly or via the alternative pathway; the C3b so formed would induce further enzyme release. This amplification system may provide an explanation for the ability of macrophages to generate mediators of inflammation and cause tissue damage and degradation at sites of chronic inflammation while retaining their ability for long periods of time.