The early phase of wound healing after small central alkali burns of the guinea pig cornea was studied using electron microscopical, enzyme histochemical, and biochemical techniques. In the first phase, which was morphologically characterized by the destruction of the epithelium and keratocytes and by the infiltration of the cornea with polymorphonuclear leukocytes, an increase in the activity of lysosomal phosphatases and glycosidases (beta-D-glucuronidase, acid beta-D-galactosidase, beta-D-N-acetylglucosaminidase) was noticed. In the second phase, the cornea was invaded by capillaries and fibroblasts. In this phase, the activity of proteases (aminopeptidase M, dipeptidyl peptidase IV) increased intra- and extracellularly, suggesting that these enzymes may be involved in the turnover of the collagenous matrix and the ground substance. Using synthetic 4-methoxy-2-naphthylamine substrates and fluorescence-band detection techniques after isoelectric focusing, an increase in the activity of endopeptidases was demonstrated. The decreased activity of gamma-glutamyl transpeptidase may be linked with the activation of latent collagenase.