The human homologue of yeast NHP2, which is known to be a core protein component of yeast H/ACA small nucleolar ribonucleoprotein particles (snoRNPs), was identified by ODD-PCR as a 313-bp cDNA fragment exhibiting a distinct decrease in its expression level during TPA-induced differentiation of promonocytic U937 into monocytes and macrophages. Sequentially, a full-length cDNA of human NHP2 was isolated and the nucleotide sequence was determined. The NHP2 gene has a predicted 153 amino acid open reading frame, encoding 17.2 kDa protein that shares 38.4% and 44.4% identity with Saccharomyces cerevisiae NHP2 and Schizosaccharomyces pombe nhp2+, respectively. The TPA-induced differentiation of U937 cells, which also resulted in growth arrest, abruptly down-regulated the expression of NHP2. Removal of TPA restored cell growth through the retrodifferentiation process and subsequent expression of NHP2. NHP2 mRNA was markedly expressed in most tumor cells including Jurkat, K562, HL-60, U937, and HeLa S3. In healthy human tissues, NHP2 mRNA was expressed at high levels in spleen, thymus, prostate, testis, ovary, small intestine, colon (mucosal lining), heart, brain, placenta, skeletal muscle, kidney and pancreas, and at low levels in liver, and very weakly in peripheral blood leukocyte and lung. NHP2 mRNA, undetectable in human peripheral T cells, was induced at a maximum level between late G(1) and S phase after polyclonal activation. The expression of NHP2 mRNA during the cell cycle progression of Jurkat T cells also reached a maximum between late G(1) and S phase. These results indicate that the human NHP2 gene may be regulated at the transcription level depending on tissue specificity and cellular proliferative status, and that the down-regulation of NHP2 expression during induced differentiation of U937 cells may result from the growth arrest accompanying the differentiation.