While human Alu repeats can be considered to be members of an extremely large, globally regulated, multigene family, each member of this family resides within a different sequence context that might uniquely modulate its transcription. Unique 3' flanking sequences for several transcriptionally active human Alu elements were identified by cDNA cloning and used for primer extension analysis to compare the basal and stress-induced expression of the corresponding Aln loci. Each of six Alu loci investigated exhibits a unique pattern of expression in three different human cell lines and in response to stress induction. The sequence context surrounding each Alu member uniquely determines its transcriptional regulation. In many cases, the individual Ain loci and total Alu RNA exhibit opposing patterns of expression implying that local rather than global regulation ultimately determines the expression of individual members. Some of the stresses, which induce Alu transcription, increase co-expression of LINE1 RNA, another requirement for Alu retrotransposition. (C) 2001 Elsevier Science B.V. All rights reserved.