Expression of DR antigen on cord blood (neonatal) human monocytes using complement-mediated cytotoxicity with anti-DR alloantisera and fluorescent-activated cell sorting (FACS) utilizing a battery of anti-DR mouse monoclonal antibodies was assessed. Forty preparations of neonatal cord blood monocytes were purified by adherence and elution from plastic petri dishes: lymphocyte contamination was less than 5% as indicated by esterase and peroxidase stains and cell sizing. By cytotoxicity tests 22 +/- 5.5% (SD) of neonatal monocytes expressed DR compared to its expression on 78.6 +/- 3.1% of adult monocytes. By FACS analysis, the frequency of DR expression on neonatal monocytes was 19-33% compared to 71-82% for adult monocytes. Incubation of neonatal monocytes with concanavalin A (Con A) or phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cell culture supernatants (lymphokine) or recombinant interferon-alpha (IFN-alpha) increased the expression of DR antigens in a dose- and time-dependent manner. A Con A-supplemented culture supernatant of unstimulated peripheral blood mononuclear cells had no effect on DR expression. Neonatal monocytes that were pretreated with anti-DR and complement in order to remove DR-positive cells were induced to express DR antigen after 2 days in culture with lymphokine. Thus DR-negative neonatal monocytes can be induced to express DR antigen. These results suggest a correctable maturational deficiency of neonatal monocytes. The inducibility of DR antigen expression by lymphokines and recombinant IFN-alpha suggests that they play an important role in the regulation of immune responses.