The human CD11a molecule is expressed specifically on lymphocytes, monocyte/macrophages, and neutrophils, in which it mediates important adhesion-related functions. We used 1.7 kb of regulatory sequences upstream from the human CD11a gene transcription start site to drive expression of a modified human CD4 reporter gene in transgenic mice. The transgene was expressed in a tissue-specific fashion on all leukocytes and paralleled endogenous mouse CD11a expression. All five founder mice expressed the transgene, providing evidence for integration site-independent expression. However, expression was not proportional to transgene copy number. These studies indicate that (1) the mutated human CD4 serves as an excellent reporter for analysis of leukocyte-specific promoters; (2) the CD11a regulatory unit used here represents a novel reagent for targeting gene expression to leukocytes; and (3) additional regulatory regions will be required for copy-number-dependent activity of CD11a regulatory sequences.