The Santa Ana Mountains, as a whole, have been well-studied floristically. Little work, however, has been conducted previously in the southwestern portion of the range which includes the San Mateo Canyon Wilderness Area of the Cleveland National Forest. This study reports the results of our floristic surveys conducted in the wilderness over a three-year period, from December 1991 through October 1994. The study area, encompassing the headwaters of the San Mateo Canyon watershed, is topographically and geologically diverse. Vegetation is characterized by a complex assemblage of chaparral and coastal sage scrub, oak woodland, native and nonnative grasslands, and riparian woodland and scrub formations. A total of 626 vascular plant taxa is reported for the wilderness, including 500 here considered native and 126 considered nonnative. Among these are 88 taxa not previously reported for the Santa Ana Mountains. Populations of 12 sensitive plant taxa are documented from the study area; these include Baccharis vanessae, Brodiaea filifolia, B. orcuttii, Chorizanthe polygonoides var. longispina, C. procumbens, Dudleya multicaulis, D. viscida, Harpagonella palmeri, Horkelia truncata, Mimulus diffusus, Polygala cornuta ssp. fishiae, and Quercus engelmannii.