Retinoic acid (RA) has been shown to increase differentiation in some leukemia cell lines (HL-60 and KG-1) but not others (K562). Similarly, RA has been reported to have variable effects on fresh blast cells. Recently, molecular clones have been obtained for the nuclear receptor for retinoic acid. The experiments described in this paper were designed to compare expression of the receptor to biological activity in myeloblastic leukemia cells. In four continuous AML cell lines, a positive correlation was found between retinoic acid receptor (RAR) expression by Northern analysis or RNA dot blot and the ability of RA to inhibit colony formation. Kinetic studies of the most sensitive cell line showed that inhibition of colony formation was associated with reduced blast cell self-renewal and differentiation-like events. RAR was detected in freshly obtained blast cells from 23 AML patients. Patient-to-patient variation was observed; however, a correlation was not found between RAR expression and response of the freshly obtained blast cells to RA.