We have cloned and sequenced several distinct loci from the human genome whose sequences agree exactly and are colinear with the sequence of the small nuclear RNA U1. There appear to be 100-150 such U1 loci in the human genome. Although these loci are not in close clusters or in small tandem repeats in the genome, the majority of them have remarkably similar genomic environments. Several potential RNA polymerase termination sites exist in the immediate 3' flanking regions of the loci studied; however, no TATA box is found in the immediate 5' flanking sequences. These observations, with the findings of others concerning the transcription of U1, suggest that U1 RNA is synthesized from a family of transcription units. These data are consistent with the proposal that RNA polymerase II may synthesize primary transcripts from these transcription units, which are processed at both the 5' and 3' ends to yield mature U1 RNA and possibly other RNA species of unknown function.