Peripheral benzodiazepine receptor (PBR) was found to be less expressed in the immature phagocytic HL-60 and U-937 cell lines than in the more mature monocytic THP-1 cell line. Cell differentiation by several agents induced a strong enhancement of PBR density on these three phagocytic cell lines but not on the lymphocytic CEM cell line. Detailed analysis of phorbol 12-myristate 13-acetate-treated THP-1 cells showed an increased PBR expression and the rise came along with an increase of CD11a and CD11b antigens and a secretion of macrophagic cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-8. Quantitation of mRNA using polymerase chain reaction (PCR)-based technique showed that overexpression of PBR did not parallel mRNA expression, indicating a gene-independent regulation. These results suggest that PBR predominance on phagocytic cells could be related to maturation process.