Collagen degradation was investigated in experimental inflammatory lesions made by implanting fluorescein-collagen sponges into sensitised rats for four days, before transferring them into culture medium. The breakdown of the collagenous structure in vitro by invading cells was inhibited by steroids and related anti-inflammatory drugs whereas non-steroidal anti-inflammatory drugs were without effect. Inhibitors of the lysosomal proteinases were variably effective with chloroquine giving total inhibition, leupeptin and TLCK partial inhibition and aurothioglucose showing no effect. Histochemical studies were made of the distribution of cathepsin B. Beta-glucuronidase and N-acetyl-glucosaminidase in macrophages attached to a collagen substratum. Measurements with specific microelectrodes showed that the microenvironment at the surface of activated macrophages was markedly acidic with values of pH less than 5 between attached cells and collagen substratum. Such conditions would be hostile to neutral collagenases and favour acid (lysosomal) proteinases.