Reductions in glycosaminoglycan(s) (GAGs) have been reported during the process of leukemia cell differentiation. It has been suggested that GAG depletion may facilitate critical membrane interactions, perhaps by exposing membrane receptors to differentiation inducers. We have investigated the effects of enzymatic removal of HL-60 cell surface GAG on maturation events. Cells treated with chondroitin ABC lyase to remove surface chondroitin sulfate, which is the major GAG constituent, did not demonstrate altered binding affinity for the differentiation inducer, 12-O-tetradecanoylphorbol-13-acetate (TPA). Similarly, a complex membrane antigen associated with maturation, the chemotactic peptide receptor, was not perturbed. These GAG-depleted cells did not spontaneously mature or have altered sensitivity to a variety of inducers. Therefore, these results suggest that surface GAG depletion does not alter the availability of surface receptors associated with the induction process.