Inappropriate leukocyte activation and disturbance of the delicate cytokine balance within the uterus during early human pregnancy may initiate spontaneous abortion. The purpose of the present study was to assess whether decidual soluble factors from women suffering sporadic spontaneous early pregnancy loss could enhance the cytotoxic activity of peripheral blood lymphocytes (PBL), and to investigate the lytic activity of endometrial granulated lymphocytes (eGL) purified from decidua against natural killer (NK)- and lymphokine-activated killer (LAK)-sensitive targets. Decidual cell culture supernatants from sporadic spontaneous abortion cases did not have any effect on PBL cytotoxic activity against the NK-sensitive target cells K562. Endometrial GL purified from decidua of spontaneous aborters were unable to lyse the LAK-sensitive target cells Raji and, in contrast with eGL from decidua of first-trimester therapeutic aborters, approximately 50% of the cases also failed to kill K562 cells. These results do not provide evidence to implicate either cell-mediated or cytokine-mediated cytolytic mechanisms in early spontaneous pregnancy loss, thus strengthening the possibility that other damaging effects are operating. Nevertheless, the deficient cytotoxic activity in a proportion of spontaneous abortion decidua merits further investigation.