Mannitol, a sugar alcohol that appears to serve as an osmoprotectant/compatible solute to cope with salt stress, is synthesized in celery (Apium graveolens L.) via the action of a NADPH dependent mannose-6-phosphate reductase (M6PR). To evaluate the abiotic stress effects of mannitol biosynthesis, we transformed celery with an antisense construct of the celery leaf M6PR gene under control of the CaMV 35S promoter. Unlike wild type (WT) celery, independent antisense M6PR transformants did not accumulate significant amounts of mannitol in any tissue, with or without salt stress. In the absence of NaCl, and despite the lack of any significant accumulation of mannitol that is normally the major photosynthetic product, antisense transformants were mostly phenotypically similar to the WT celery. However, in the presence of NaCl, mature antisense transgenic plants were significantly less salt-tolerant, with reduced growth and photosynthetic rates, and some transformant lines were killed at 200 mM NaCl, a concentration that WT celery can normally withstand. Although mannitol biosynthesis is normally enhanced in salt-treated WT celery, no such increase was observed in the antisense transformants. Like our previous gain of function results showing enhanced salt tolerance in Arabidopsis plants transgenic for a sense M6PR construct, these loss of function results, using an antisense construct in celery, demonstrate a major role for mannitol biosynthesis in developing salt-tolerant plants.