We report experimental interspecific hybridization between Anastrepha fraterculus (Wiedemann), A. sororcula Zucchi, and A. obliqua (Macquart), widespread and highly destructive crop pests in the Neotropical region. Prezygotic reproductive isolating mechanisms (such as different mating times and male calling songs) seem to be easily disrupted in no-choice crossing conditions, and hybrid flies can be obtained in both directions in most crosses. Crosses between A. sororcula females and A. fraterculus males and between A. obliqua females and A. sororcula males yield adult offspring of males and females. Crosses between A. fraterculus or A. sororcula females and A. obliqua males yield only females, clearly obeying Haldane’s rule (preferential inviability or sterility of heterogametic hybrids). Crosses between A. obliqua females and A. fraterculus males and between A. fraterculus females and A. sororcula males yield poor or no adult offspring of both sexes, with a few exceptions. Most F₁ hybrids are fertile and can be backcrossed to both parental species. The few morphological diagnostic characters of the parental forms appear intermediate in F₁ hybrids. In addition, we describe some morphological abnormalities found in hybrids, attributed to maternal or cytoplasmic effects, and the occurrence of gynandromorphs in the progeny of one cross.