Low levels of fruit production are thought to threaten the persistence of Asclepias meadii (Mead's milkweed) populations. We evaluated four hypotheses explaining the low fruit production in one population (herbivory, pollen limitation, resource shortages and rainfall) by collecting within-year data on stem size, levels of fruit initiation and mature fruit production and by considering among-year data on total fruit production and annual rainfall. In 2002, severe herbivory resulted in the death of about 63% of the population's flowering stems. Managers could increase fruit production by protecting stems from mammal herbivory. A path analysis revealed that leaf width and the number of fruits initiated were the most important predictors of mature fruit production. In 1991–2002 the previous year's total annual precipitation significantly affected the total number of fruits produced only in years of burning. Increasing the persistence of these long-lived plants to years of greater rainfall could have the most dramatic effects on fruit production and on survival of the species.