A systematic literature review from 1966 to 2000 revealed 2,730 English-language publications on the role of bacteria in human primary dental caries in vivo. The most pertinent 313 papers were analyzed in evidence tables accessible online (http://www.nidcr.nih.gov). The search targeted all bacterial types implicated previously in caries and asked two questions. First, what is the association of specific bacteria with tooth decay and can causation be attributed to any of those bacteria? Retrieved studies were categorized as randomized-blinded-interventional, longitudinal, case-control, and cross-sectional and were weighted in descending order in terms of significance. Although many studies, due to ethical requirements, had confounding variables, they still indicate strongly: 1) the central role of the mutans streptococci in initiation of caries of smooth surfaces and fissures of crowns of teeth and suggests their potent role in induction of root surface caries; and 2) that lactobacilli are implicated as important contributory bacteria in tooth decay, but their role in induction of lesions is not well supported. Second, what is the source of infection by cariogenic bacteria? Molecular/genetic studies of implicated bacteria isolated from humans, randomized-blinded-interventional, and longitudinal studies indicate that mutans streptococci are spread vertically among humans, mostly from mothers to their children. Implications of these conclusions are briefly discussed. The most significant problems of literature interpretation include the benefits/shortcomings of salivary and plaque monitoring of the flora, the role of sugar(s) in decay as it influences the flora, and modeling strategies to predict lesion score increments as distinct from determination of the etiological role of specific bacteria. Future directions for microbiological clinical caries research are suggested, and the use of the term "caries" to describe the disease, not its lesions, is urged.