Summary• In small isolated populations, genetic drift is expected to increase chance fixation of partly recessive, mildly deleterious mutations, reducing mean fitness and inbreeding depression within populations and increasing heterosis in outcrosses between populations.• We estimated relative effective sizes and migration among populations and compared mean fitness, heterosis, and inbreeding depression for eight large and eight small populations of a perennial plant on the basis of fitness of progeny produced by hand pollinations within and between populations.• Migration was limited, and, consistent with expectations for drift, mean fitness was 68% lower in small populations; heterosis was significantly greater for small (mean = 70%, SE = 14) than for large populations (mean = 7%, SE = 27); and inbreeding depression was lower, although not significantly so, in small (mean = )0.29%, SE = 28) than in large (mean = 0.28%, SE = 23) populations.• Genetic drift promotes fixation of deleterious mutations in small populations, which could threaten their persistence. Limited migration will exacerbate drift, but data on migration and effective population sizes in natural populations are scarce. Theory incorporating realistic variation in population size and patterns of migration could better predict genetic threats to small population persistence.