The existence of receptors for opioid compounds on cells of the immune system has long been hypothesized, but has been very difficult to demonstrate unequivocally. We have used reverse-transcription polymerase chain reaction to obtain cDNA clones from the human MOLT-4 and CEM-3 T-leukemic cell lines which are nearly identical to portions of the δ and κ opioid receptor cDNAs recently isolated from human brain and placenta, respectively. Northern analyses with riboprobes derived from the δ and κ opioid receptor clones indicate these sequences are expressed at low levels in human peripheral blood lymphocytes and in several human lymphoid cell lines. Sequences corresponding to the μ opioid receptor cDNA were not detected in this study. These results suggest that δ and κ opioid receptors may be responsible for mediating some direct effects of opioids in immune cells.