The full expression of Class 1 antigens of the major histocompatibility complex (HLA A,B,C,) on ocular cell surfaces appears to be developmentally regulated; HLA is undetectable in retina from 16-week-old fetal eyes but is present in adult retina. Cultured retinoblastoma (RB) may serve as a useful model of retinal cell development. SF81 is an undifferentiated subculture of in vitro retinoblastoma with little evidence of spontaneous differentiation and lack of expression of HLA, attesting to the "undifferentiated" character of this cell line. RB SF81 cells were treated with retinoic acid, a known stimulator of differentiation (optimal concentration 5 X 10(-8) M). HLA expression was evaluated with immunofluorescence, immunoperoxidase, and radioimmunoassay, using monoclonal antibodies. RB SF81 treated with retinoic acid showed a significant, persistent increase in HLA levels by 24 hours compared with controls. Thus, retinoic acid has been documented to induce the surface expression of HLA in undifferentiated retinoblastoma. Developmental parallels between embryonic retina and in vitro retinoblastoma treated with retinoic acid exist.