Prostaglandins are reported to play an important regulatory role in cell-mediated immunity. The immunosuppressive properties of a new synthetic oral prostaglandin E1 analogue, misoprostol, were studied in vivo in a rat heterotopic cardiac allograft model, and in vitro in mixed lymphocyte reaction. The results show that parenteral misoprostol, alone or in combination with low dose cyclosporin immunosuppressive therapy, significantly prolonged cardiac allograft survival compared with appropriate controls. Oral misoprostol alone in this model did not allow for measurable cardiac allograft prolongation. In vitro misoprostol demonstrated significant dose-response inhibition of the mixed lymphocyte culture assay. It is concluded that new prostaglandin E1 analogues with oral bioavailability may have important applications to clinical transplantation in man, and may be cyclosporin sparing.