B-myb and c-myb expression is high in neuroblastoma cells and declines during retinoic acid-induced differentiation. We show here that B-myb down-regulation during retinoic acid-induced differentiation of LAN-5 neuroblastoma cells occurs at the transcriptional level. In addition, we measured B-myb and c-myb messenger RNA half-lives, and found that, unlike c-myb, B-myb messenger RNA was remarkably stable (> 10 h). Inhibition of protein synthesis by treatment with cycloheximide increased B-myb messenger RNA levels, suggesting that one or more labile proteins act as repressors of B-myb transcription. In the same cell line, blocking protein synthesis decreased the level of c-myb mRNA under both normal and differentiative conditions. Thus, B-myb and c-myb undergo similar transcriptional regulation, but there are specific differences in the stability of their messenger RNAs and in the mechanisms through which their transcription is controlled. These differences could reflect different functional roles played by c-myb and B-myb in neuroblastoma cells.