The fate of successive and simultaneous male to female skin isografts has been studied in an isohistogenic strain of rats. Single 1 cm2grafts had a mean survival time of 61.8 days. Two and four simultaneous grafts to individual hosts survived for a similar length of time. The survival times of second grafts applied 7 or 14 days after first grafts did not differ significantly from that of first grafts. Graft survival times were significantly shortened in rats which received second grafts 21 or 86 days after first grafts or after complete destruction of first grafts. The time of onset of the reaction against the grafts, as judged by macroscopic appearance, varied greatly. Differences in the time of onset of the reaction were observed between grafts residing on different hosts but also between grafts residing on the same host. Variance analysis showed that differences between hosts were the major source of variation. It is suggested that these differences between hosts are related to the hosts' specific immunological responsiveness. By contrast, the considerable variation in the time required for completion of graft destruction may be independent of this factor.