Ancestrally continental forest species of the tribe Oryzomyini, the endemic cricetid rodents of the Galápagos, have had to adapt to the harsh tropical desert of the Islands. Following the recent rediscovery of the Santiago nesoryzomys (Nesoryzomys swarthi) endemic to Isla Santiago, Galápagos, we conducted the 1st autecological study of this species. Our 3-year study revealed mean annual survival of 23.2% and maximum survival of 812 days. Reproductive activity was restricted to the wet season with a stable annual proportion of breeding females and a consistent peak in pregnancy in April. The likelihood of postpartum breeding increased with rainfall when 2 litters were produced. The growth and development of juveniles was slow and they did not reproduce in their natal year. Positive correlations between rainfall and mean adult body weight and between vegetation density (particularly prickly pear cactus [Opuntia galapageia]) and population levels supported a hypothesis of food limitation. Comparisons with the Galápagos oryzomys (Oryzomys bauri), endemic to Isla Santa Fe, and a review of continental members of the tribe Oryzomyini suggest that the ephemeral, unpredictable environment of the Galápagos arid zone has selected for a strategy of relatively high survival and low reproduction in N. swarthi and O. bauri that is more typically found among the desert Heteromyidae than other members of the Oryzomyini. We also present data on sex ratio, home range, and philopatry that together indicate a promiscuous or polygynous mating system. Our findings may help to guide future conservation strategies for this endangered rodent species.