It has been shown that a high dose administration of human intravenous immunoglobulin G (IVIG) prolonged the survival time of xenografted guinea pig heart in the rat. In this study, we compared the effectiveness of intact IVIG (I-IVIG), Fc fragments of IVIG (Fc-IVIG), and F(ab') fragments of IVIG (Fab-IVIG) in preventing xenogenic hyperacute rejection in the guinea pig-to-rat heart transplantation model. Relatively high dose administration of IVIG (0.6 g/kg body weight) induced xenograft survival times of 32.0 +/- 13.0 min and 33.2 +/- 16.8 min with I-IVIG and Fab-IVIG, respectively, which were significantly longer than times for animals treated with Fc-IVIG or for untreated control animals (survival times of 12.6 +/- 7.4 min and 10.4 +/- 7.6 min, respectively). The in vitro inhibitory effect of guinea pig red blood cell hemolysis by fresh rat serum correlated with the results of in vivo study. On the other hand, the in vitro inhibitory effect of IVIG on pig red blood cell hemolysis by fresh human serum showed that Fc-IVIG, which had little effect in the guinea pit-to-rat combination, had a higher inhibitory effect than Fab-IVIG, or I-IVIG. Fc-IVIG and I-IVIG achieved a complete inhibition of in vitro hemolysis in the pig-to-human combination. It is suspected that an interference with the complement classical pathway by the Fc portion of IVIG could be an attractive tool for inhibition of hyperacute rejection in the pig-to-human combination.