Six-week-old honey mesquite [Prosopis glandulosa (Torr.) var. glandulosa] seedlings were treated with various concentrations of ethephon (2-chloroethylphosphonic acid) and 2,4,5-T [(2,4,5-trichlorophenoxy)acetic acid] alone and in combinations to determine effect on stem mortality under greenhouse conditions. Ethephon alone at 0.05 g/L brought about defoliation and a reduction in xylem tissue formation but did not affect the histological development of the stem tissue. Treatment with 2,4,5-T alone at 3.2 g/L resulted in 40% stem mortality along with the formation of abnormal xylem tissue of reduced thickness. A combination of ethephon (0.05 g/L) and 2,4,5-T (3.2 g/L) significantly increased mesquite mortality. This was associated with a further reduction in xylem thickness, abnormal development of the xylem, abnormal positional relationships of vascular tissues, and initiation of adventitious roots. This study showed that ethephon in combination with 2,4,5-T was more effective than either treatment alone in promoting the disruption of the tissue systems of the stem and in increasing control of mesquite seedlings.