Loefling's Iter Hispanicum (1758) and its subsequent translations, editions, issues, and facsimiles are analyzed for their impact on the nomenclature of American vascular plants. The book, edited by Linnaeus and posthumously published, contains descriptions of plants found in Venezuela (as well as in the Iberian Peninsula). For American plants the original volume (1758) is the source of 31 new genera, 15 new species, and one replaced name, and a German translation (1766) is the source of an additional two new species. Many of these nomenclatural innovations have been ignored, overlooked, or intentionally suppressed, some for centuries. Other names in the Iter Hispanicum have been misinterpreted. We examine the reasons for considering these 49 names to be validly published and the nomenclatural ramifications. In the interests of nomenclatural stability we are forced to conclude that the names of at least ten taxa described by Loefling should be rejected: Ayenia sidiformis Loefl., Cofer Loefl., Cruzeta Loefl., Cruzeta hispanica Loefl., Edechia inermis Loefl., E. spinosa L., Justicia putata Loefl., Menais Loefl., Muco Loefl., and Samyda parviflora Loefl. Likewise the names of two species described by Linnaeus that are tied to the Iter Hispanicum should be rejected: Menais topiaria L. and Spermacoce suffruticosa L. Finally, we select neotypes for Gaura fruticosa Loefl., Salvinia michelii Loefl., and Waltheria melochioides Loefl.