Plaque samples from interproximal surfaces were obtained on floss from 164 young men. The sample site was between the upper first molar and second premolar on the right side, with the criterion that clinical caries was absent. Radiographs were taken. A total of 83 lesions were found on radiographs and Streptococcus mutans was positive (+ +) in 72% of the associated cultures. In 81 participants no lesions were found and S mutans was not present in 46% of the cultures (− −). The hybrid situation of lesions in the absence of positive cultures (+ −, 28%) could be explained by experimental error, lesion arrestment, sampling error, or presence of some other cariogenic bacteria. The hybrid situation of no lesions and positive cultures (− +, 54%) could be explained by the presence of very early caries activity or the presence of some noncariogenic strain S mutans. However, a strong positive correlation occurred between early detectable lesions and S mutans; this leads to the conclusion that the bacterium is associated with interproximal caries.