Regulation of myeloblastin expression was studied during myeloid differentiation of HL60 cells and compared with that of myeloperoxidase. Induction towards the monocytic pathway of differentiation caused a rapid, marked and parallel down-regulation of both transcripts which were insensitive to cycloheximide. Thus, myeloblastin is directly regulated and, similarly to myeloperoxidase, belongs to the set of primary response genes. Nuclear run-on experiments and RNA half-life determinations revealed that myeloblastin regulation was at both the transcriptional and posttranscriptional levels.