This study is an investigation of genetic variation among the CODIS (combined DNA index system) STR (short tandem repeat) reference collections. The analysis was conducted in two parts. The first is an overall comparison (G-test) of allelic frequency distributions for 12 STR loci among 19 forensic databases representing various major groups and ethnic populations. In the second phase of the study, the impact of database replacement on DNA profile frequencies and inclusion probabilities is examined. The G-test results reveal clear allelic frequency differences among the major divisions, and, in some cases, among ethnically distinct subdivisions of the same major group affiliation. Other results indicate that database substitution may sometimes lead to substantial alterations in individual inclusion probabilities. Furthermore, there are numerous instances in which an allele present in some databases is missing in others. Fortunately, in most cases, these effects may not be forensically significant due to the increased discriminatory power of the STR markers employed in the CODIS system. However, differences in inclusion probabilities may become critical in situations in which DNA quantity is severely limited and/or compromised by degradation since, in these cases, the power of forensic STR analysis may be mitigated by reducing the number of informative loci.