An accumulation of data from in vitro to in vivo model system has established a pivotal role of three crucial ligand activated nuclear receptors RXR, LXR-alpha and VDR for their ability to regulate an array of genes involved in regulation of fundamental cellular processes to patho-physiological situations. Keeping in view RXR as a common heterodimeric partner for LXR-alpha and VDR, the present study was designed to dissect the interrelationship between these three nuclear receptors in peripheral blood mononuclear cellular model. The present study revealed that all the three nuclear receptors displayed auto regulation in response to their specific ligands; Both LXR-alpha and VDR regulated the expression of their heterodimeric partner RXR; and VDR was regulated by LXR-alpha through its ability to modulate SREBP response element present in the promoter region of VDR gene. Based on these findings, the role of these nuclear receptors could be better understood in various nuclear receptor mediated pathological processes.