Functional L1 elements are autonomous retrotransposons that can insert into human genes and cause disease. To date, 10 of 12 known L1 retrotranspositions into human genes have been found to be 5"-truncated and incapable of further retrotransposition. Here we report the nucleotide sequences of the two full-length L1 elements, L1beta-thal and L1RP, that have inserted into the beta-globin and retinitis pigmentosa-2 (RP2) genes, respectively. L1beta-thal is 99. 4% identical to a consensus sequence of active human L1s, while L1RP is 99.9% identical. Both elements retain impressive capacity for high frequency retrotransposition in cultured HeLa cells. Indeed, L1RP is the most active L1 isolated to date. Our data indicate that not all L1 insertions into human genes are 'dead on arrival'. Our findings also lend further credence to the concept of cis preference, that the proteins encoded by a particular L1 preferentially act upon their encoding RNA as opposed to other L1 RNAs.