The histopathology of human root caries was examined in extracted teeth by different optical methods. The present part of the study details the sequential stages of initial caries in both cementum and peripheral dentin. Significant differences are shown between the mechanisms operating on the various dental hard tissues during development of caries. Histologically distinguishable reaction patterns depended on both the degree of the cariogenic challenge and the respective structural features of cementum and peripheral dentin. Earliest lesions, histologically visible as small clefts traversing cementum and extending into peripheral dentin, were clinically not detectable. Cementum was stepwise destroyed until peripheral dentin became exposed. The exposed peripheral dentin was sclerosed and tubule-free. Demineralization of dentin preceded the degradation of the organic matrix. Frequently, a hypermineralized layer occurred in both cementum and exposed dentin. Its localization was not identical with the anatomical surface. Initial penetration of bacteria into peripheral dentin occurred along small clefts. Breakdown of the organic matrix was the final step in the destructive phase of the carious process.