APOBEC3G (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G) is an innate intracellular antiretroviral factor that can inhibit viral retroelements such as retroviruses and hepadnaviruses. However, it is unknown whether it can act on non-viral substrates. Retrotransposons are transposable elements that cumulatively account for about one third of the human genome. They are commonly classified in long terminal repeat (LTR) retrotransposons, which are strongly homologous to retroviruses, and non-LTR retrotransposons also known as L1 elements or LINE-1 (long interspersed nucleotide element-1) elements. Most of the L1 elements are defective and only a small number are very active in vivo, but they are responsible for nearby all of the retrotransposition in the human population. The cloning of active human L1 elements has allowed the development of tissue culture-based assays for measuring their retrotransposition potential. We used such an assay to demonstrate that APOBEC3G, which impairs the replication of exogenous retroelements, does not affect the replication of endogenous L1 retrotransposons.